BioPharm

www.biopharminternational.com March 2018 BioPharm International eBook 19 Outsourcing Resources Quality Agreements ing capabilities," and noted that it uses a contract facility. Its contract facility happened to be located at the same address and shared per- sonnel with the distributor. FDA put the firm on import alert and sent a warning letter saying, "it is important to note that quality agreements cannot be used to dele- gate statutory or regulatory respon- sibilities to comply with CGMP." In another recent case, an owner contracted out product release test- ing, but failed to ensure that the contract testing lab's methods were validated. FDA issued a warning letter to the owner saying, "Your quality assurance agreement with [contract facility] does not specify method validation responsibili- ties. … You and [contract facility] have a qualit y assurance agree- ment regarding the testing of your products. You are responsible for the quality of drugs you produce, regardless of agreements in place with your contract testing labora- tory. You are required to ensure t hat d r ugs a re made i n accor- dance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, and purity." WHEN THE CONTRACT FACILITY ERRS FDA investigators found that a contract manufacturing facilit y had shipped drugs to the United States without expiration dates. In response to the FDA 483 observa- tions, the firm said, "As we under- st a nd, ou r c u stome r s conduc t testing to confirm stability and expiration dating." The firm also responded that it was contacting its customers to confirm respon- sibilities and OTC drug product expiration dating. FDA put the company on import alert and sent a warning letter with a courtesy copy to the owner. In this example, the contract facility made a bad assumption. This illustrates why all parties must be aware of their roles and responsibilities to ensure adul- terated product is not marketed. In another example, FDA cited a contract facilit y making OTC drugs with numerous violations the same as or similar to those in past inspections, such as failure to validate processes and failure to verify the suitability of analyti- cal methods. In its warning letter, FDA told the firm, "FDA is aware that many pharmaceutical product manufacturers use independent contractors, such as production facilities, testing laboratories, pack- agers, and labelers. FDA regards contractors as extensions of the manufacturer. You are responsible for the quality of drugs you pro- duce, regardless of agreements in place with product owners. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, and purity." WHEN BOTH PARTIES VIOLATE CGMP In one recent matter, both the o w n e r a n d c o n t r a c t f a c i l i t y received warning letters explain- i n g t he i r sh a r e d r e s p on sibi l i- ties. The contract facilit y used the same facilities and equipment for manufacturing toxic car-care products and oral solution drugs and received an FDA warning let- ter citing three CGMP violations. FDA also sent a warning letter to the product owner, saying, "You are responsible for ensuring that all your products are manufac- tured in accordance with CGMP, including oversight of the man- ufacturing operations conducted by your contrac tor … on your behalf. Contractors are extensions of the manufacturer, and you are required to ensure that your drugs are made in accordance with sec- tion 501(a)(2)(B) of the FD&C Act." In another situation, FDA found that an owner and contract facility had released product even though neither the owner nor the contract facility had conducted release tests. The FDA warning letter said, "You explained to our investigator that you make finished product release decisions over the phone with your contract manufacturer, based on whether test results meet pre-estab- lished specifications … During the inspection, you confirmed that your contract manufacturers do not make your OTC drug products in conformance with drug CGMP. For example, you have released some drugs for which neither you nor your contract manufacturers conducted release tests for identity and strength of active ingredients. As a result, some of your drugs are distributed without confirma- tion that they meet specifications for identity and strength of their active ingredients." 'WE DIDN'T THINK WE NEEDED TO SHARE THAT INFORMATION' Issues can arise through the failure to communicate a product quality issue. In this example, a contract facility was producing bottles of a sterile solution. Over a four-year period, it received more than 1500 complaints about leaking, under- filled, and empty bottles. The firm i nvest igated a nd at tempted to correct the problem, but failed to notify the owner about the com- plaints. In its warning letter, FDA said, "Your failure to follow the provisions of your quality agree- ment and appropriately notify your customer of the quality problems discussed in this letter may have delayed your customer's ability to take important actions to ensure the quality, safety, and efficacy of its products, including notifying FDA via a field alert report (FAR) under 21 CFR 314.81."

• Cover