Meg, from one of my parenting forums, redacted this from the FDA’s letter about the Tylenol, Benedryl, Motrin and Zyrtec recall. This is long but please read all the way through so you can understand why many parents are outraged — and maybe you will be too. All the following problems were cited at a facility in Pennsylvania. More information about the recall is here. Meg’s post follows:
The FDA’s letter is 17 pages long. I have gone through each of the FDA’s “observations” and given the highlights of McNeil’s transgressions. Also note that this is the ONLY facility that makes the brand name liquid pediatric medications (Tylenol, Motrin, Benadryl, Zyrtec), including those distributed to hospital and clinics for “official” use, so odds are good your child has been exposed to some of this at some point.
This is a very long post and I’m going to truncate it, but feel free to slog through if you want the shocking details (and I say that sincerely, since obviously I am not selling a magazine at the checkout stand or anything! :p)
If you want to copy and paste this elsewhere, feel free. I think the public needs to know this! So far the news agencies have just hit on “voluntary recall” and this is so, so much more than that…
The responsibilities and procedures applicable to the quality control unit are not fully followed.”
The raw materials used to produce Children’s and Infant’s Tylenol contained “known contamination of gram negative organisms.” Furthermore, their Quality Assurance and Complicance Department was “deficient” in that it does not maintain “adequate laboratory facilities,” it is “default in investigations,” etc. In other words: bacteria were going into drugs intended for sick infants and children, they knew it, and they didn’t care.
There are no 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.”
When the batch of Infant’s Dye-Free Tylenol was increased in size, they failed to adjust the manufacturing process (“agitation and tank time level”).
Control procedures fail to include adequacy of mixing to assure uniformity and homogeneity.”
See above. This is why some products contained more or less active ingredient than they should have.
Control procedures are not established which monitor the output and validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product.”
They did not have an adequate quality control system in place to identify or address the above issues.
Written production and process control procedures are not followed in the execution ofproduction and process control functions.”
There were “46 consumer complaints regarding foreign material, black or dark specks from June 2009 to April 2010” and the company failed to document or proceed adequately.
There is a failure to thoroughly review any unexplained discrepancy whether or not the batch has been already distributed.”
After some of the end-of-run samples were tested and found inadequate, the products were sent to market anyway. If other batches made under the same conditions were already on the market, they were not investigated to see if they were also inadequate.
GMP training is not conducted with sufficient frequency to assure that employees remain familiar with CGMP requirements applicable to them.”
“Specifically, employees are not given training in current good manufacturing practices and written procedures required by current good manufacturing practice regulations…”
Employees started work before being trained, including the “Change Parts Coordinator [who] did not receive training on [redacted]… [yet s/he] is
responsible for cleaning and maintaining tooling in the Compression tool room.”
Procedures describing the handling of all written and oral complaints regarding a drug product are not followed.”
They received complaints that Infant’s Dye Free Tylenol had a “lack of effect” yet no investigation was conducted.
Each container of component dispensed to manufacturing is not examined by a second person to assure that the weight or measure is correct as stated in the batch records.”
“Specifically, Infant’s Tylenol Suspension Drops, Cherry… A mixup occurred and a partial drum weighing less than the required amount was used instead of the correct drum.”
Thus, sub-potent Infant Tylenol made it to market.
Strict control is not exercised over labeling issued for use in drug product labeling operations.”
Labeling is supposed to be stored “in a locked cage with limited access.” But in this facility, “labeling was observed to be stored throughout the warehouse accessible to all warehouse operators and personnel that have access to the raw material/component storage warehouse.”
There is no written testing program designed to assess the stability characteristics of drug products.”
Expiration dates were thus more or less arbitrarily assigned, since they had no written guidelines explaining how the drugs would be tested for shelf stability. The expiration dates were not based on any uniform scientific data or testing of the products. Some testing was done on some of the runs, but the “samples are not representative samples” because they were taken only from the beginning of the run– not the middle or end.
Laboratory controls do not include the establishment of scientifically sound and appropriate test procedures designed to assure that components and drug products conform to appropriate standards of identity, strength, quality and purity.”
The products and raw materials were NOT tested for any type of mold, yeast, or “other potential known environmental contaminants found in the manufacturing facility and/or raw materials.” They tested only for certain microbes (and, as we know from earlier in the report, largely discounted those results anyway.)
Adequate lab facilities for testing and approval or rejection of components and drug products are not available to the quality control unit.”
This is where things begin to get more heinous, in my opinion. It discusses a particular air filter that “failed the specification of penetration” and “leakage at the frame.” They failed to conduct an “aerosol challenge installation leak test” to ensure that contaminants could not enter the “Walk-In Chambers, refrigerator and freezer room.” They failed to properly calibrate a filter.
Furthermore, there was “no cleaning/use log for the [redacted] used for raw material weighing.” There was “[t]hick dust covering the grill inside the [redacted] filtered cabinet.” “No identification of the temperature probes in [redacted]. Duct Tape wrapping the copper piping insulation inside the [redacted] where the firm stores water samples and refrigerated media. Incubator [redacted] had a large amount of visible grey and brown dust/debri [sic] observed on the bottom of the chamber… where media filled containers… were located.” There was a “large exposed hole (gap) in the ceiling” above an incubator and next to an air vent.
Many of the laboratory equipment items had “out of service” dates. They had failed to check or recalibrate a “water sample refrigerator… pH meter… shaker incubator… culture incubator.”
These “deviations” were observed during testing of Children’s Zyrtec Sugar Free Syrup. The testing was performed in a vacuum hood. The hood “had about a 6 inch silicon plug located on the right side upper [redacted] filter.” One side of the hood had a “very large spider-like crack… where the vacuum hose was located. This vacuum hose is not used.” Furthermore, the “microbiologist was observed to pour media… placed in front of the larger 250 mL bottle, which blocked/disrupted the [redacted] air flow.” The same microbiologist was “observed to open media… close to the outside of the hood rather than inside the hood.” S/he “was observed to spray hands and items in the hood with [redacted] Disinfectant Scented Spray directed into the [redacted] filter.” S/he “was obsered to spray the outside wrapped items placed in the hood, which were opened outside of the hood rather than inside the hood. For example, pipettes used to transfer product with [redacted] to the plates.”
And “[g]rills in front of the entire face of the [redacted] filters in Hood #s [redacted] were plastic with ~one inch diameter squares and not easily sanitized/cleaned. Hood [redacted] grill was dirty with grime in each square and missed pieces of plastic in several locations on the plastic grill.”
Laboratory records do not include complete records of the periodic calibration of laboratory instruments, gauges, and
This included “laboratory refrigerators” which were “not calibrated adequately” until “04/22/10” (which is presumably when this FDA inspection occurred.)
Written specifications for laboratory controls do not include a description of the sampling procedures used.”
Standard Operating Procedures must identify the dilution level, the number of colonies of bacteria observed, the type of swab used for sampling (e.g. cotton, etc.) They failed to do this.
Samples taken of in-process materials for determination of conformance to specifications are not representative.”
For instance, “[r]aw material… samples pulled by the manufacturer… is not a statistically significant… representative sample of the total.”
Each lot of components was not appropriately identified as to its status in terms of being quarantined, approved or rejected.”
There were no “[s]eparate or defined areas to prevent contamination or mix-ups… related to the storage of released components.” Thus, any product put aside for being rejected was not labeled or segregated or differentiated in any way from the products approved for market.
They also observed “Corn Starch… leaking powder from one bag.”
Several products “were observed stored in cardboard boxes on a pallet… ‘Bad cartons’ had been handwritten in black ink on the cardboard boxes. The cartons were in unrestricted status…”
One of the stock rooms and one Restricted Storage Room “located in the microbiological laboratory had excess media in boxes and special projects stored in the room with no designated area of storage for approved, quarantine, or rejected status. The room was cluttered with boxes of media, special projects that had bins with various containers of chemicals, special projects with boxed finished OTC products, boxes of computer items, out of service equipment, etc. Until 04/23/10, the firm had no inventory of the room contents.”
Components are not microscopically examined when appropriate.”
The written procedure of the company is to test their water supply for microbial contaminants weekly and/or monthly. The FDA found “no monthly trend reports.”
Records are not kept for the maintenance and inspection of equipment.”
This included issues such as “hoses on the [redacted] were said to NOT be dedicated to products processed on these two fluid bed dryers” (emphasis in the original.) “In addition, the person verifying that cleaning was performed [redacted] on 04/17/10 was a temporary person from a different McNeil site and lacked training on [redacted].”
Additionally, “[s]eals on the [redacted] were observed to be in disrepair and not maintained with several cracks.” “Inlet air insulation was wrapped with peeling masking-like tape.” “No documentation on cleaning and maintenance of the Microbiological Laboratory… as required.” “[Redacted] was observed to contain a large about of visible grey and brown material on the filter behind the grill.”
The persons double-cbecldng the cleaning and maintenance are not dating and signing or initialing the equipment cleaning and use log.”
There was “[n]o second signature verifying that maintenance was completed” as required.
There you go. Join in our outrage.