Inspections, Compliance, Enforcement, and Criminal Investigations

Pocono Coated Products LLC 10/27/16

  

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 Atlanta District Office
60 Eighth Street N.E.
Atlanta, GA 30309 

October 27, 2016

VIA UPS
RETURN RECEIPT REQUESTED
 
Ms. Susan Myer, Owner
Pocono Coated Products, LLC
100 Sweetree St.
Cherryville, NC 28021-3066
 
WARNING LETTER
(17-ATL-01)
 
Dear Ms. Myer:
 
 
The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Pocono Coated Products LLC, at 100 Sweetree St., Cherryville, NC, October 26 - 30, 2015. This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 CPR Parts 210 and 211. Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 50l(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).
 
We acknowledge receipt of your November 17, 2015, written response and have reviewed it in detail. During our inspection, our investigators observed specific violations including, but not limited to, the following:
 
1.    Your firm does not have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)).
 
You released finished drug products (b)(4) to your customer without conducting or reviewing release testing to determine if your products conformed to their specifications.
 
FDA collected samples of (b)(4) at your customer, (b)(4). FDA laboratory analysis indicated that the drug was sub-potent for (b)(4). The product label claim is (b)(4), while our analysis indicated results of (b)(4) (below the limit of quantitation). Based on this analysis, on March 23, 2016, your customer, (b)(4), recalled all lots of (b)(4) within expiry.
 
Your written quality agreement with (b)(4), indicates that (b)(4) is responsible for final product release to the market. The same agreement also states that Pocono is responsible for release of products to the customer, but you did not conduct any laboratory analysis to determine whether your products conformed with specifications prior to releasing them to (b)(4).
 
According to your response, your ongoing corrective actions included a final inspection form, work instructions, guidance documents, and checklists to assure quality approval before you release product to owners. You did not specify if you were going to test your product prior to release.
 
In response to this letter, describe your corrective action plan to assure satisfactory conformance to specifications for your active ingredients and drug products prior to release.
 
2.    Your firm failed to establish written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).
 
Our inspection revealed that your firm failed to validate the manufacturing process for the (b)(4) and other transdermal patches. Documented successful process validation shows that each step of a manufacturing process is controlled and provides confidence that the finished product meets all quality attributes, including specifications. FDA test results demonstrating that your product was subpotent indicate that your un-validated manufacturing process is not capable of consistently delivering products that meet their specifications.
 
See FDA's guidance document, Process Validation: General Principles and Practices, for FDA's current thinking on elements of process validation at http://www.fda.gov/downloads/Drugs/.../Guidances/UCM070336.pdf.
 
In response to this letter, provide your complete process validation plan, including the interim steps you will take to ensure the quality of your drug products prior to completing your validation activities.
 
3.    Your firm failed to determine actual yields and percentages of theoretical yield at the conclusion of each appropriate phase of manufacturing (21 CFR 211.103).
 
Your master batch records lacked a statement of theoretical yield, percentage of theoretical yield, and statements of limits beyond which an investigation is required. Without calculating theoretical yield, you may be missing important indications of possible error throughout your manufacturing process.
 
In your response, you state you will now calculate actual yield versus theoretical yield for subbatches. You also stated you will use (b)(4)" as the investigational limit for yield deviations. This response is inadequate because you have not explained the scientific rationale for using this limit for yield deviations.
 
In response to this letter, provide detailed information regarding how you will calculate theoretical and actual yield in your manufacturing processes, as well as the scientific rationale for the yield limits you set that would trigger an investigation under 21 CFR 211.192.
 
4.    Your firm failed to establish written procedures for the preparation of master production and control records designed to assure uniformity from batch to batch (21 CFR 211.186(a). Your firm also failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced (21 CFR 211.188).
 
Our inspection found that you lack written procedures for preparing master production records. The master batch record for (b)(4) lacked information critical to the manufacturing process, including machine operating parameters (e.g., milling, mixing, and drying time ranges), ingredient target ranges, a sampling plan, and specifications.
 
Furthermore, the batch records for (b)(4) and (b)(4) showed inconsistent times for milling and mixing; no specified drying time; and inconsistent amounts of added ingredients.
 
According to your response, you began generating "Master Production Records/Work Instructions" for all aspects of CGMP manufacturing after our inspection. Your response is inadequate because you did not include an assessment of the potential risks for batches that you released without complete data regarding their conformance with specification. As noted above, FDA testing found that some of products you released to your customer were sub-potent.
 
In your response to this letter, summarize the changes you have made to your master batch record. Include a risk assessment of how these deficiencies may have affected the quality of the drug products you released within expiry.
 
CGMP Consultant Recommended
 
Based upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant, qualified as set forth in 21 CFR 211.34, to assist your firm in meeting CGMP requirements. Your use of a consultant does not relieve your firm's obligation to comply with CGMP. Your firm's executive management remains responsible for fully resolving all deficiencies and ensuring ongoing CGMP compliance.
 
Conclusion
 
Violations cited in this letter are not intended to be an all-inclusive list. You are responsible for investigating these violations, for determining the causes, for preventing their recurrence, and for preventing other violations. Correct the violations cited in this letter promptly. Failure to promptly correct these violations may result in legal action without further notice including, without limitation, seizure and injunction. Unresolved violations in this warning letter may also prevent other Federal agencies from awarding contracts.
 
Until these violations are corrected, we may withhold approval of pending drug applications listing your facility. We may re-inspect to verify that you have completed your corrective actions. We may also refuse your requests for export certificates.
 
After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done since our inspection to correct your violations and to prevent their recurrence. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.
 
Send your response to Ingrid Zambrana at the address above. If you have any questions about the contents of this letter, contact Jose R. Lopez, Compliance Officer, at 787-729-8603 or by email at joser.lopez@fda.hhs.gov. Please identify your response with FEI 3011029136.
 
Sincerely,
/S/
Ingrid A. Zambrana  
District Director
Atlanta District Office
Southeast Region, Office of Regulatory Affairs
U.S. Food and Drug Administration
 
Cc:
(b)(4)
 
Cc:
Mr. Richard G. Myer
Chief Operating Officer
Pocono Coated Products, LLC
100 Sweetree Street
Cherryville, NC 28021-3066

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