Erin Brockovich preparing to help - Gardasil adverse events

[WillYourVoteBCounted]

Gardasil

August 6, 2008

We have been spending our days getting all our ducks armed for bear and in a row--all of our anti-Gardasil ducks, that is. From checking my various areas on the internet, to finding moderators to listening to the tragic and painful stories of victims of the Gardasil vaccine, it has been a very busy time for me and my team.

Gardasil, as you should know by now, is an HPV vaccine sold by MERCK, a vaccine with a flawed marketing campaign targeting young girls. The premise is that the vaccine will protect young girls from cervical cancer, as well as a couple of varieties of HPV. But the vaccine is NOT a cancer preventative, and it has not been thoroughly tested. Not only does Gardasil not protect everyone, it does not prevent all types of cervical cancer. According to current science, there are fifteen types of HPV associated with cervical cancer but Gardasil only counters HPV types 16 and 18. The vaccine requires three doses to start and scientists don't even know how frequently boosters will be needed. They don't know because they did not adequately research this before putting the vaccine out on the market using our young girls as guinea pigs.

MERCK was even pushing to have this untried vaccine REQUIRED by states. Governer Perry of Texas--who bypassed the state legislation with an executive order--has ties to Merck. Mike Toomey, Perry’s former chief of staff is one of the drug company’s three lobbyists in Texas. The governor also received $6,000 from Merck’s political action committee during his re-election campaign. "Merck is bankrolling efforts to pass state laws across the country mandating Gardasil for girls as young as 11 or 12." As a mother, should I have to sign a waver to protect my daughter from having a potentially dangerous vaccine forced on her?
...
The Vaccine Adverse Event Reporting System (VAERS) now has 7195 individual adverse reactions listed--and as it is a database not everyone knows about, not all of the adverse reactions are being reported. The Centers for Disease Control report over 9,000 adverse reactions for Gardasil. There is a rising total of deaths connected with the administration of this vaccine; as well as have been reports of seizure activity, tingling, numbness and loss of sensation in the fingers and limbs. There is serious question about girls initially having short-term health problems associated with getting this vaccine that could turn into long-term neurological or immune system disorders; and there is serious question about administering this vaccine at the same time as others.

...If you or a loved suffered a serious adverse event, such as death, disability or blood clot following the administration of Gardasil, please contact me [e-mail] . I will have one of our staff of experienced attorneys review your claim to advise you about your rights.

Erin Brockovich

[varkam]

1. I guess you missed my post about the VAERS database, huh?

Shame.

Mrs. Brockovich's post on the matter is also fairly disengenuous. Let's have a look-see:

Gardasil, as you should know by now, is an HPV vaccine sold by MERCK, a vaccine with a flawed marketing campaign targeting young s. The premise is that the vaccine will protect young s from cervical cancer, as well as a couple of varieties of HPV. But the vaccine is NOT a cancer preventative, and it has not been thoroughly tested. Not only does Gardasil not protect everyone, it does not prevent all types of cervical cancer. According to current science, there are fifteen types of HPV associated with cervical cancer but Gardasil only counters HPV types 16 and 18. The vaccine requires three doses to start and scientists don't even know how frequently boosters will be needed. They don't know because they did not adequately research this before putting the vaccine out on the market using our young s as guinea pigs.

Of course, I'm not sure what Mrs. Brockovich would consider being thoroughly tested, but Gardasil did go through all three stages of pre-approval testing. In Phase III, alone, more than 12,000 women were followed for two years following the administration of Gardasil.

While Mrs. Brockovich is technically accurate in claiming that "according to current science, there are fifteen types of HPV associated with cervical cancer...only counters HPV types 16 and 18", it is also disengnuous in that the types of HPV that Gardasil is meant to protect against are associated with upwards of 70% of all cervical cancer cases.

MERCK was even pushing to have this untried vaccine REQUIRED by states.

The question of whether or not the vaccine is safe and effective, and the question of whether or not the vaccine should be mandated are two different questions entirely. In my mind, the burden of proof that one has to satisfy in order to justify a vaccine being added to the routine schedule of vaccination is higher than for simple approval from the FDA for a medicine to be released to the market. In my mind, I'm not sure if that burden is met.

The Vaccine Adverse Event Reporting System (VAERS) now has 7195 individual adverse reactions listed--and as it is a database not everyone knows about, not all of the adverse reactions are being reported. The Centers for Disease Control report over 9,000 adverse reactions for Gardasil. There is a rising total of s connected with the administration of this vaccine; as well as have been reports of seizure activity, tingling, numbness and loss of sensation in the fingers and limbs. There is serious question about girls initially having short-term health problems associated with getting this vaccine that could turn into long-term neurological or immune system disorders; and there is serious question about administering this vaccine at the same time as others.

As I had posted recently, the VAERS database is only intended to be a "canary in the coal mine", and not to be used as evidence for a causal relationship between the administration of a vaccine and adverse reactions to the vaccine. For example, one researcher was able to enter into VAERS that the flue vaccine turned him into The Hulk. Had that researcher not agreed to have that AE removed from VAERS, it would still be listed.

All that is not to say that VAERS doesn't have a utility - it does - but going ahead and mining data from it (such as what the Geiers did in some of their famously bad research on autism) isn't going to get you any closer to the truth.

The FDA Vaccine Adverse Effect Reporting System has more than 8,000 incidents associated with Gardasil. The most serious complications reported include death and the development of blood clots.

The CDC says that they have not ruled-in one case of death as attributable to the Gardasil vaccine. That's not to say that it hasn't happened or that it is not possible, but that there is simply little to no basis for claiming it as of yet.

[WillYourVoteBCounted]

2. You get really upset when anyone criticizes the Gardasil vaccine

n/t

[varkam]

3. Lame.

Try again!

[WillYourVoteBCounted]

4. you have a real hard on for my threads

EVERY TIME I POST A THREAD, YOU TRY TO TEAR IT DOWN. YOU POST REPEATEDLY
OVER AND OVER AND OVER SAME OLD SHIT EVERY TIME.

WHY THE BIG HOTS FOR MY THREADS?

[varkam]

5. I don't know.

I really should have give up by now - all you seem to be good at is name-calling, ad hominem arguments, and ignoring the substantive issues that are raised.

In fact, I'm not sure if, in the nonsense that you've posted over the past few days, you have never replied to a post of mine without doing one of the above. I mean, you're welcome to change that now if you want to - please, feel free to go back to my original reply and respond to the issues that I raised if you would like.

:shrug:

Or you can keep flinging poo at me. Your call.

[beam me up scottie]

6. This is a forum for discussion and debate.

If you are unprepared or unable to defend your opinions here you really should find another soapbox.

[trotsky]

7. Your Caps Lock is stuck.

Might want to fix that.

You have yet to demonstrate you understand what VAERS is. We don't want your ignorance to spread.

[cosmik debris]

8. The facts deserve equal time.

Your mythology should not dominate the conversation just because you can type in all caps.

[Celebration]

9. Amercian College of Pediatricians statement

http://acpeds.org/?CONTEXT=art&cat=10006&art=140&BISKIT=2170483

Currently, an HPV vaccine is approved for children and adults ages 9-26. Despite encouraging results in prelicensure studies, research definitively establishing the duration of HPV vaccine protection, degree of protection and spectrum of side effects remain to be determined.

This was a 2007 statement. Has their position changed?

Apparently it was only tested in 1,121 girls under 15, yet that is who they are vaccinating. What was the reason for that? Why would testing be done mainly on a population that is not targeted for treatment?

I can't think of a good reason why the aluminum adjuvant was the only "placebo" studied. Has the safety of the adjuvant been the subject of FDA safety trials?

http://www.medscape.com/viewarticle/565691_3

During the last 15 years, a syndrome called macrophagic myofasciitis has been associated with aluminum-adjuvanted vaccines. Most cases have been reported in France and most of the patients have been adults,<32> but there are also descriptions of cases in other countries and in children.<33> The patients have presented with a variety of clinical symptoms, but usually they include myalgias, arthralgias, fatigue and, in some cases, serious neurological diseases, such as MS. Muscular biopsies have, in several cases, been taken from the deltoid region because of the symptoms. The biopsies have shown macrophages surrounding the muscle fibers forming a characteristic histological lesion. Electron microscopy has shown the presence of aluminum hydroxide inclusions in the lesions.<34> The patients have all been vaccinated with different aluminum-containing vaccines from months to years before the biopsy was taken.

[WillYourVoteBCounted]

10. good pt. Still, Mom's report girls are gettting large warts after getting vaccinated

I have read accounts by parents of their daughters developing large and deep warts on their arms and legs after having the vaccine.

Also, one of the factories in the US that manufactures Gardasil was cited for having some contamination in the drugs/ingredients.

I put that on my other thread (Gardasil Side Effects) where the same three people who had a hard on for attacking my threads - did everything they could to distract from that and other posts.

The fact is, some healthy girls are becoming sick or dead girls after getting this vaccine, sometimes within hours of getting the vaccine.

The vaccine may injure or kill more girls than it claims it would save.

BUT, Merck will make over $300 per girl, injured or not, since Merck has been "vaccinated" against
lawsuits over Gardasil.

[trotsky]

11. Maybe you could actually address the counter-arguments

instead of just dismissing facts that dispute your position as "people who had a hard on for attacking my threads"?

[Celebration]

12. Theirs was not such a ringing endorsement

It pretty much sounds like an ongoing experiment--

[Celebration]

13. Aluminum adjuvant linked to gulf war illness induces motor neuron death in mice.

Since this vaccine has aluminum hydroxide in it, and because aluminum hydroxide was actually used as a control group, perhaps it is the adjuvant causing some of the problems.

http://www.ncbi.nlm.nih.gov/sites/entrez

Mice didn't do too well when injected with aluminum adjuvant at the same dose level as Gulf War veterans.

[WillYourVoteBCounted]

14. Ingredients in Gardasil include yeast & Borax/roach killer

In addition to using aluminum as an adjvant, there are some other ingredients to be concerned about.

Anyone who is allergic to the ingredients of Gardasil should not receive the vaccine.

Gardasil is fermented in giant vats of yeast paste, which means that anyone with a yeast allergy should not get the vaccine. The CDC's Vaccine Information Statement lists yeast allergy as a reason to avoid the vaccine, but the Patient Product Information on gardasil.com does not specifically mention yeast.

CDC info on HPV vaccination:
Some girls or women should not get HPV vaccine or should wait

Anyone who has ever had a life-threatening allergic reaction to yeast, to any other
component of HPV vaccine, or to a previous dose of HPV vaccine should not get the
vaccine. Tell your doctor if the person getting the vaccine has any severe allergies
http://www.cdc.gov/vaccines/Pubs/vis/downloads/vis-hpv.pdf

Merck info on HPV vaccination (does not list yeast):
The listed ingredients are: "purified inactive proteins that come from HPV Types 6, 11, 16, and 18…amorphous aluminum hydroxyphosphate sulfate, sodium chloride, L-histidine, polysorbate 80, sodium borate, and water for injection."
http://www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_ppi.pdf

Sodium Borate:

Borax (from Persian burah), also known as sodium borate, sodium tetraborate, or disodium tetraborate, is an important boron compound, a mineral, and a salt of boric acid. It is usually a white powder consisting of soft colorless crystals that dissolve easily in water.
Borax has a wide variety of uses. It is a component of many detergents, cosmetics, and enamel glazes. It is also used to make buffer solutions in biochemistry, as a fire retardant, as an anti-fungal compound for fiberglass, as an insecticide, as a flux in metallurgy, and as a precursor for other boron compounds.

http://en.wikipedia.org/wiki/Sodium_borate

Here is what the medical encyclopedia of the U.S. National Library of Medicine and the NIH has to say about sodium borate, another ingredient in Gardasil:

Sodium borate is the main ingredient in boric acid. (Powdered boric acid is often used to kill cockroaches.)

Sodium borate poisoning can be acute or chronic. Acute, accidental sodium borate poisoning usually occurs when someone swallows powdered roach-killing products that contain the chemical.

Poisoning may also occur in those who are repeatedly exposed to sodium borate. In the past, boric acid was used to disinfect and treat wounds. Patients who received such treatment over and over again got sick, and some died. Because boric acid is now known to be a dangerous poison, it is no longer commonly used in medical preparations. However, boric acid is contained in some vaginal suppositories used for yeast infections, although this is NOT a standard treatment.

http://www.nlm.nih.gov/medlineplus/ency/article/002485.htm

[WillYourVoteBCounted]

15. Package insert: Gardasil has Aluminum, Yeast, Borax & Polysorbate

Package insert was Ingredients in Gardasil include Yeast & Borax and Polysorbate .. Polysorbate can cause allergic reactions as well.

Package Insert

DESCRIPTION

GARDASIL * is a non-infectious recombinant, quadrivalent vaccine prepared from the highly purified
virus-like particles (VLPs) of the major capsid (L1) protein of HPV Types 6, 11, 16, and 18. The L1
proteins are produced by separate fermentations in recombinant Saccharomyces cerevisiae and selfassembled into VLPs. The fermentation process involves growth of S. cerevisiae on chemically-defined fermentation media which include vitamins, amino acids, mineral salts, and carbohydrates.

The VLPs are released from the yeast cells by cell disruption and purified by a series of chemical and physical methods.

The purified VLPs are adsorbed on preformed aluminum-containing adjuvant (amorphous aluminum
hydroxyphosphate sulfate). The quadrivalent HPV VLP vaccine is a sterile liquid suspension that is
prepared by combining the adsorbed VLPs of each HPV type and additional amounts of the aluminum containingadjuvant and the final purification buffer.

GARDASIL is a sterile preparation for intramuscular administration. Each 0.5-mL dose contains
approximately 20 mcg of HPV 6 L1 protein, 40 mcg of HPV 11 L1 protein, 40 mcg of HPV 16 L1 protein,
and 20 mcg of HPV 18 L1 protein.

Each 0.5-mL dose of the vaccine contains approximately 225 mcg of aluminum (as amorphous
aluminum hydroxyphosphate sulfate adjuvant), 9.56 mg of sodium chloride, 0.78 mg of L-histidine,
50 mcg of polysorbate 80, 35 mcg of sodium borate, and water for injection. The product does not containa preservative or antibiotics.

After thorough agitation, GARDASIL is a white, cloudy liquid

http://www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf

POLYSORBATE:

in "multiple medical preparations (eg, vitamin oils, vaccines, and anticancer agents) "
"Polysorbate 80 is a ubiquitously used solubilizing agent that can cause severe
nonimmunologic anaphylactoid reactions. "

http://www.ingentaconnect.com/content/acaai/aaai/2005/00000095/00000006/art0001\;jsessionid=1oas93idk52v4.victoria

[varkam]

16. Your link takes me to the PubMed homepage.

Got an abstract or something?

[Celebration]

17. here

http://www.ncbi.nlm.nih.gov/pubmed/17114826

Gulf War illness (GWI) affects a significant percentage of veterans of the 1991 conflict, but its origin remains unknown. Associated with some cases of GWI are increased incidences of amyotrophic lateral sclerosis and other neurological disorders. Whereas many environmental factors have been linked to GWI, the role of the anthrax vaccine has come under increasing scrutiny. Among the vaccine's potentially toxic components are the adjuvants aluminum hydroxide and squalene. To examine whether these compounds might contribute to neuronal deficits associated with GWI, an animal model for examining the potential neurological impact of aluminum hydroxide, squalene, or aluminum hydroxide combined with squalene was developed. Young, male colony CD-1 mice were injected with the adjuvants at doses equivalent to those given to US military service personnel. All mice were subjected to a battery of motor and cognitive-behavioral tests over a 6-mo period postinjections. Following sacrifice, central nervous system tissues were examined using immunohistochemistry for evidence of inflammation and cell death. Behavioral testing showed motor deficits in the aluminum treatment group that expressed as a progressive decrease in strength measured by the wire-mesh hang test (final deficit at 24 wk; about 50%). Significant cognitive deficits in water-maze learning were observed in the combined aluminum and squalene group (4.3 errors per trial) compared with the controls (0.2 errors per trial) after 20 wk. Apoptotic neurons were identified in aluminum-injected animals that showed significantly increased activated caspase-3 labeling in lumbar spinal cord (255%) and primary motor cortex (192%) compared with the controls. Aluminum-treated groups also showed significant motor neuron loss (35%) and increased numbers of astrocytes (350%) in the lumbar spinal cord. The findings suggest a possible role for the aluminum adjuvant in some neurological features associated with GWI and possibly an additional role for the combination of adjuvants.

[varkam]

18. Do you know what the specific dose was? eom

[Celebration]

20. no, not more than what I posted

It was to be an animal model for the amount given to Gulf War veterans.

[varkam]

24. Well, according to the insert...

the vaccine given to vets had about 2.4 mg of aluminum in it whereas Gardasil has about 225mcg in it. 2.4mg is roughly ten times greater a concentration than 225mcg. Given that the dose makes the poison, I'm not entirely sure what conclusions one can draw from comparing the two.

[WillYourVoteBCounted]

19. FDA letter to Merck Vaccine Plant r/e violations in April 28, 08

FDA Home Page | Search FDA Site | FDA A-Z Index | Contact FDA



Department of Health and Human Services

Public Health Service
Food and Drug Administration
Rockville, MD 20857

April 28, 2008

WARNING LETTER


OEWL-08-02

EXPRESS MAIL
Richard T. Clark
President and Chief Executive Officer
Merck and Company, Inc.
770 Sumneytown Pike
West Point, Pennsylvania 19486-004

Dear Mr. Clark:

The Food and Drug Administration (FDA) conducted an inspection of Merck and Company, Inc., West Point, Pennsylvania, between November 26, 2007, and January 17, 2008. During the inspection, the FDA investigators documented significant deviations from current good manufacturing practice (CGMP) in the manufacture of licensed biological vaccine products, bulk drug substances, and drug components. These products include Liquid PedvaxHIB®, RECOMBIVAX HB®, ProQuad®, Gardasil®, VAQTA®, and COMVAX®. These deviations from CGMP include non-compliance with Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the requirements of your biologics license application approved under Section 351 of the Public Health Service Act (PHS Act), and Title 21, Code of Federal Regulations (21 CFR) Parts 210 and 211.

At the close of the inspection, the FDA investigators issued a Form FDA 483, Inspectional Observations, which described a number of significant objectionable conditions relating to your firm’s compliance with CGMP. Significant deviations observed during the inspection include, but are not limited to, the following:

CGMP DEFICIENCIES CONCERNING DRUG PRODUCTS

1. You failed to thoroughly investigate any unexplained discrepancy of a batch or any of its components to meet any of its specifications whether or not the batch has already been distributed and to extend the investigation to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy 21 CFR 211.192. For example:

a. You submitted a Biological Product Deviation Report to FDA in October 2006, due to the redacted of Varivax III being out-of-specification at the two month stability time point. This product had been shipped to redacted and then returned to the United States before being placed on stability. The product was not licensed in the United States at the time of the deviation. Your investigation concluded that the failure was due to the ingress of redacted into the vial headspace during shipment redacted. Your investigation did not include testing of other potentially affected products shipped redacted, for example, ProQuad®, to determine if there were any detrimental effects on these products.

b. Numerous customer complaints have been received citing over-pressurization of vials. For example, Complaints 48891 and 53106 for Zostavax®, lot redacted, concerned over-pressurization of vials. The investigations did not address the possibility of redacted ingress as the reason for over-pressurization of vials. The investigation also did not consider the possibility that the packing method might not be functioning as validated.

c. Not all lots of product that may have been affected by fibers being shed from redacted lot redacted were assessed. Only redacted lots of product, where the fibers were observed during filling, were quarantined and assessed. Approximately redacted lots of lyophilized product and redacted lots of liquid products were filled during the time of receipt and use of redacted lot redacted.

d. Product lots that failed the initial redacted visual inspection for critical defects such as redacted and redacted were not thoroughly investigated. For example, MMR II® lots redacted and redacted failed the critical defect category for redacted and no investigations were performed. These lots were subsequently distributed.

2. You failed to establish adequate written procedures describing the handling of all written and oral complaints regarding a drug product 21 CFR 211.198. For example, Standard Operating Procedure (SOP) 283-316, redacted directs that a lot history be performed. This lot history is performed for the final finish lot number, which is the packaging/labeling lot number. However, complaints such as leaking vials/syringes and various container/closure defects would be associated with a fill lot number, and a fill lot number may be associated with several final finish lot numbers.

3. Your firm failed to assure that there are written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess 21 CFR 211.100(a). For example:

a. The validation performed in December 2006 for redacted machines 2, 3, and 4 is not representative of the actual automated inspection process for detection of redacted defects, in that there was no assessment of acceptably filled vials. This equipment is used to inspect multiple vaccine products from filling lines 131 and 138.

b. Process control limits were not evaluated and re-established for filling line defects for Zostavax® as required by SOP 300-103X. The SOP states that the Process Control Limits (PCL) should be evaluated after the first redacted lots and again after redacted lots or sooner if changes were made to the process. Redacted lots were inspected by the redacted from February 2006 to September 2007, yet the limits have not been evaluated.

4. You failed to assure that equipment used in the manufacture, processing, packing and holding of a drug product is calibrated, inspected, or checked according to a written program designed to assure proper performance 21CFR 211.68(a). Specifically, a set of control samples representing defect types are examined by the automated inspection equipment prior to beginning each inspection process. The reject set testing allows high rates of known rejects to be accepted by the equipment. In addition, the first time non-accepts are sent back through the equipment and only those rejected a second time are discarded.

5. You failed to exercise appropriate controls over computer or related systems to assure that changes in master production are instituted and input and output from the computer or related system of formulas are checked for accuracy and maintained 21 CFR 211.68(b), in that there is no documentation to support software manufacturing change performed to the redacted used in the manufacture of Gardasil®, lots redacted and redacted.

6. You failed to establish test procedures or other laboratory control mechanisms designed to assure that drug products conform to appropriate standards of identity, strength, quality, and purity and to assure that any deviation from the written test procedures or laboratory control mechanisms shall be recorded and justified 21 CFR 211.160(a) and (b). For example:

a. During review of atypical process reports (APR’s), QA release personnel may edit the number of occurrences calculated by the software. This practice is not addressed in the product release SOP. In addition, the practice has been used inconsistently. The number of occurrences is reportedly decreased if the root causes of the multiple deviations are not related; however, the opposite logic was applied to nine test failures for VAQTA®. These nine test failures, although related, were recorded as a single occurrence in the deviation tracking system.

b. CP 9110.001, redacted does not direct that any anomaly concerning the product or sample preparation such as leaking vials or test canisters, over-pressurized vials, or particles be documented on the testing worksheet. The procedure only addresses foreign material in test media and the inability to reconstitute lyophilized product. In these cases, the instructions are to notify the supervisor.

c. There are no data to support extension of expiration for preservative-free RECOMBIVAX HB® Reference Standard Lot redacted to redacted years, as redacted year stability data are not yet available.

CGMP DEFICIENCIES CONCERNING BULK DRUG SUBSTANCES AND DRUG COMPONENTS

Additionally, significant deviations in manufacture of your bulk drug substances and drug components were observed during the inspection. These deviations cause your bulk drug substances and drug components to be adulterated within the meaning of Section 501(a)(2) (B) of the FD&C Act. Specific areas of concern include, but are not limited to:

Production and Process Controls

1. You failed to assure that there are written production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. For example:

a. SOP 209-205X, redacted allows for a maximum of three re-dispensing operations prior to filling. To date, there have been no stability studies initiated for redacted re-dispensed bulk.

b. There are no data to support the redacted post redacted hold time for tanks used in the redacted Manufacturing Complex redacted. Specifically, the tanks used for media challenges to support the redacted post redacted hold were not equivalent to the PedvaxHIB® processing tanks. The tanks used are redacted with redacted while the PedvaxHIB® tanks have redacted with redacted. Additionally, the tanks used in PedvaxHIB® production include assemblies that are connected to the tank and redacted in place.

Failure Investigations

2. Failures are not fully investigated and documented, nor extended to other batches as appropriate. For example:

a. You failed to quarantine numerous process intermediates associated with the use of redacted filter membranes that were identified to cause foaming during filtration. This foaming was found to be associated with leaching of redacted into process intermediates. These process intermediates were used to further manufacture MMR®II, PedvaxHIB®, VAQTA®, VARIVAX® product lots.

b. Your investigation into leaks discovered in the redacted during redacted recharge for lot redacted concluded that the leaks resulted from a small hole in the redacted. The investigation also concluded there was no impact “due to the isolation of the leak and immediate remediation of the leak.” Attached to the investigation was an unsigned and undated chronology of events, estimated to the second. This information was derived from a notebook maintained by the production operator. However, these pages from the notebook are no longer available.

c. APR 2006-204C-0034 dated 8/24/2006 was issued for the sterility failure of Pedvax bulk lot redacted. The contaminant was noted as redacted. The investigation failed to assess a recent change in the SIP cycle for redacted tank redacted in redacted. The validation of this SIP change was subsequently implicated during investigation of the failure of a redacted media challenge, which led to the recall of several PedVaxHIB® and COMVAX® lots.

Laboratory Controls

3. Laboratory controls do not include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure components and products conform to appropriate standards of identity, strength, quality and purity. For example, there has been no evaluation of the stability of redacted measles, mumps and rubella drug components over the multiple year storage and use periods. Existing stability data for the drug components are limited to potency of the vaccine components and sterility testing.

Building and Facilities

4. Written procedures for the use of cleaning and sanitizing agents designed to prevent contamination of your facility are incomplete. Specifically, SOP 204-608X, redacted does not provide a frequency for performance of the multi-step decontamination with redacted.

Maintenance of Equipment

5. Written procedures are not followed for the maintenance of equipment used in manufacture, processing, packing or holding. Specifically:

a. Work order 1400076, dated August 29, 2007, issued for the 6-month maintenance on the PedvaxHIB® redacted tank redacted, required a check of the condition of the redacted. This action was documented as "NA". However, there was no documentation as to why this prescribed action was not completed.

b. Work order 1415800, dated September 9, 2007, issued for the annual maintenance of the PedvaxHIB® redacted on redacted, documented the first (10) inspections on the work order as "NA". However, there was no documented reason for the failure to complete these activities.

Containers and Closures

6. You failed to assure that container closure systems provide adequate protection against foreseeable external factors in storage and use that can cause deterioration or contamination of bulk drug substances and sterile solutions used in production. For example:

a. Study FR #99-053, redacted did not include an assessment of the effect of storage conditions. This container/closure is used for bulk drug substances including Pedvax®HIB, RECOMBIVAX®, and redacted.

b. Redacted sterile filtered solutions used in the manufacture of vaccines are stored in containers for redacted. Validation studies have not been conducted to assure container/closure integrity.

The deficiencies described in this letter are indicative of your quality control unit’s inability to fulfill its responsibility to assure the identity, strength, quality, and purity of your drug product and drug substance.

We acknowledge receipt of your written response dated February 15, 2008, which addresses the inspectional observations on the Form FDA 483 issued at the close of the inspection, and we have reviewed its contents. Corrective actions addressed in your letter may be referenced in your response to this Warning Letter; however, we believe that your response(s) did not provide sufficient detail to fully assess the adequacy of the corrective actions. Our comments and requests for further information regarding corrective action are detailed below. The items correspond to the observations listed on the Form FDA 483:

Observation 2
Your response indicates that although direct testing of other products susceptible to redacted ingress was limited in scope, there was no detrimental affect on product potency and/or sterility. However, your investigation states that impact to vaccine potency for MMR can not be extrapolated from the results obtained for the Varivax III product. In addition, your investigation states that due to the limited redacted capacity of the ProQuad® single dose product (04984-00), redacted impacts the vial headspace and the resulting lower redacted upon reconstitution. Please provide an explanation to clarify these statements.

Observation 3
Please note that the investigation report dated December 20, 2007, for MMR Lot redacted is referred to as the final investigation report in the letter preceding the report. This report was also presented to the investigator as the Final Manufacturing Investigation. Alternatively, you refer to this report in your response as “a summary of your comprehensive investigation…in response to the request from redacted. Please explain if this is a final report or a summary of the final report.

Observation 14
Your response did not provide any documentation of the inputs and outputs generated during your investigation of the incident that caused the omission of the coding observed during the manufacture of Gardasil® lots. Additionally, your response did not include an explanation of the code, which controls the updates and downloads in the redacted. Observation 15

In your response you state “Independent of the high antigen content, an analysis of the Enzyme ImmunoAssay (EIA) method indicates that it is performing within historical parameters….” you also state that the findings from your investigation to date conclude that: “The EIA was underestimating the antigen content at the redacted step. This measurement is used to determine the antigen concentration taken into the redacted.” As these statements seem to contradict each other, please provide a detailed explanation to clarify these statements.

Observation 16
In your response you acknowledge the importance of effective glass management in vial filling areas and the need to ensure that the line clearance procedures address the removal of broken glass from critical processing areas and equipment. We acknowledge the formation of a Glass Breakage Management Team and the issuance of a guidance document entitled, “Management of Glass Breakage,” on October 15, 2007. Please provide an update relating to your divisional glass breakage initiative. Please include the status of the three action items mentioned at the end of your response to this observation.

Observation 18
Your response seems to be adequate and will be followed up at the next inspection. However, we noted that during the inspection, information was given that does not correlate with the information in your response. During the inspection, your production supervisor indicated that the redacted system recorded the data but that there was no review of the monitoring data collected by the system. Also, at two different times during the inspection your production supervisor was unable to provide any information to explain the cited pressure losses.

Observation 20 C
Your response indicates that no marketed product has been manufactured with measles drug components held for more than redacted years and that all measles drug components in inventory at or greater than redacted years have been quarantined. However, your response does not address how the potency out-of-specification stability result will affect the expiration dating of measles drug components and vaccine drug products made from these drug components. Please comment.

Observation 25
Your response stated that independent of the validation of redacted #2 and #3 for volume of fill, there was no impact to product quality for all lots produced since there is an additional 100% manual inspection for redacted. Please provide the procedure(s) in place prior to and after the current inspection covering the 100% manual inspection for volume of fill.

Observation 34
Your response states that you have verified that none of the data entry errors impacted the redacted leak test results or resulted in the incorrect use of the redacted within your manufacturing areas. Furthermore, you state that you conducted and completed a thorough investigation into the root cause for these errors and you list several corrective actions that will be implemented to address the causes. Please provide information on how you verified the redacted leak test results or that no redacted were used in manufacturing. Additionally, the investigation and relevant documents as well as the updated SOPs you mention in your response should be available for review at the next inspection.

Observation 37
Your response included the same historical data for two of the markers redacted in CP9110.780 and the Historical Reference Curve ed 50 Values in CP9110.780) that were reviewed during the inspection. Furthermore, updated data submitted in support of the historical redacted parameter in CP9110.780 continue to show a downward trend with respect to the upper and lower control limits. These data are also inadequate to support the expiry extension. Commitments to evaluate the expiry date for the November 2006 and November 2007 extensions (based on historical performance evaluation markers) and update the extension parameters in SOP 129.022 redacted are noted; however, these do not address the problems with IVRP assay. Please provide the results from the investigation of the 48 month stability time point investigation and additional information regarding storage of the gold standard reference material (Lot redacted).

Observation 38
Your response indicates that you will establish a redacted re-evaluation date on redacted based on the supplier’s redacted years stability data at redacted. If this critical reagent has a re-evaluation date, please explain your criteria for extending the date. Also, please clarify whether or not the redacted is stored at -20 ?C and whether there is data to support the redacted year storage at redacted.

Observation 43
Your response indicates that by March 31, 2008, you will have established the following: 1) a procedure clearly defining those individuals that had authority to delete tests in redacted (would coincide with modification of redacted users accounts) and what documented approvals would be required prior to deletion of a test; and 2) a report which will summarize all deleted tests, which will be reviewed and approved by laboratory management and then forwarded for approval to the Director/Associate Director of Product Release on a monthly basis. Copies of the relevant SOPs as they relate to your enhancements regarding test deletions and reports summarizing all deleted tests should be available for review at the next inspection. Finally, it was stated during the inspection that your firm was also going to conduct an evaluation of the need to assess all pharmaceutical products to confirm that all release tests were performed. What is the status of that evaluation?

Neither this letter nor the observations noted on the Form FDA 483, which were discussed with you at the conclusion of the inspection, are intended to be an all-inclusive list of deficiencies that may exist at your facility. It is your responsibility as management to assure that your establishment is in compliance with the provisions of the Federal Food, Drug, and Cosmetic Act, Public Health Service Act, all applicable federal laws and regulations, and the standards in your license. Federal agencies are advised of the issuance of all Warning Letters about biological products so that they may take this information into account when considering the award of contracts.

To facilitate your remediation efforts we request a meeting with you and other senior management at Merck to further discuss the issues cited in this letter and your proposed responses to address them. Given the potential contributions of safe, pure, and potent vaccines to the public health, we encourage frequent interactions between your technical staff and FDA in an effort to help Merck move forward with corrective actions as rapidly as possible.

Please notify this office in writing, within 15 working days of receipt of this letter, of any steps you have taken or will take to correct the noted violations and to prevent their recurrence. Include any documentation necessary to show that correction has been achieved. If corrective actions cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed. Failure to promptly correct these deviations may result in regulatory action without further notice. Such actions may include license suspension and/or revocation, seizure or injunction.

Your response should be sent to Food and Drug Administration, Office of Regulatory Affairs/Office of Enforcement/Division of Compliance Management and Operations, HFC-210, 15800 Crabbs Branch Way, Rockville, Maryland 20855.

If you have any questions regarding this letter, please contact Jacqueline Little, Ph.D., Team Biologics Compliance, Division of Compliance Management and Operations, at [phone]. To schedule a meeting at your earliest convenience, please telephone Julie D. Bringger, Compliance Officer, Team Biologics Compliance, at [phone], ext. 104, to discuss an appropriate date and time for the meeting.


Sincerely,

/S/

David K. Elder
Director
Office of Enforcement

Office of Regulatory Affairs

[WildClarySage]

21. She CLEARLY has no financial motivation

unlike teh evul Merck. :eyes:

[cosmik debris]

22. That's right!

Their "staff of experienced attorneys" are all working pro bono and won't accept any of the settlements from "deep pockets" Merck.

I wonder how long Ms. Brockovich would be interested if there were no "deep pockets" involved?

[Celebration]

23. Exactly why we have judges and juries!!

Generally both sides have financial or other interests, so thus we have the court system.

[varkam]

25. Which would mean something if the OP was a court ruling. eom

[Celebration]

26. Definitely would mean a lot more!!

Still, it is an interesting post about a "might be" court case.