On August 7 last year, the US Food and Drug Administration (USFDA) had “strongly” recommended Biocon Limited to engage a “qualified” third party consultant (TPC) to evaluate operations at its Bengaluru facility, which had received 10 adverse observations from the regulator in June. Subsequently, on August 10 and August 16, the firm assured the USFDA that it has “already proactively engaged qualified TPCs” and will continue to bring on board additional external consultants and experts as needed.
The August 7 e-mail by a USFDA official to four Biocon executives had stated: “Based on the violations we identified at your firm, we strongly recommend that you engage a qualified TPC to evaluate your firm’s operations (including your quality management system) and assist your firm in meeting CGMP (current good manufacturing practice) requirements for aseptic processing.” On November 20, 2017, the USFDA gave a clearance to the Bengaluru facility and closed its inspection. Biocon earned approximately 22 per cent of its revenues from the US in 2016-17.
According to an executive of a Mumbai-based pharma firm, the USFDA recommends engaging a TPC for resolving specific compliance issues when it feels that the firm’s internal team does not have the capability to do the same. Some major TPCs in the Indian pharma sector are Lachman Consultants, Parexel, Greenleaf Health and Princeton Group. “USFDA officials generally do not want to engage in too much of back and forth … They want to keep their work load as light as possible. That is when they recommend TPCs,” An executive at a prominent TPC said. Indian Pharmaceutical Alliance (IPA), an organisation of top Indian pharma firms, did not respond to specific queries about TPCs.
Another senior executive of a top pharma firm said: “When FDA finds that the internal compliance team is not capable of taking the corrective and preventive actions or there is insufficient skill in the organisation or there are repeated violations of GMPs (good manufacturing practices), or the company is granted consent decree for serious GMP issues, they generally recommend working with TPC for a process called compliance remediation.”
The consent decree is an agreement between FDA and the pharma company that usually bars the latter from manufacturing and distribution until it can prove, through a TPC, that it has achieved and can maintain regulatory compliance. In response to specific queries of The Indian Express, the Biocon spokesperson stated: “Biocon, in its statement to stock exchange on November 20, 2017, has confirmed that the USFDA has issued an Establishment Inspection Report (EIR) in relation to the CGMP inspection of its aseptic drug product facility that was audited between May 25 and June 3. The USFDA has classified the outcome of this inspection as VAI (“voluntary action indicated”) and the EIR states that the inspection is closed”
The spokesperson added: “Subsequently, Biocon’s press release on December 1, 2017 has confirmed that our product biosimilar Trastuzumab (for breast cancer) manufactured at this facility has received approvals from USFDA, thus becoming the first biosimilar Trastuzumab developed in India to be approved in the US. This indicates that the regulatory agency has accepted the responses and commitments submitted by us, including implementation of our corrective and preventive action plans. Hence, there is no outstanding issue open with the regulator in this regard.”
At the end of his August 7 email, the USFDA official said: “Verify the effectiveness of your corrective actions via a thorough follow-up evaluation conducted by a TPC…The evaluation should cover your manufacturing operations and your quality management system, and help to assure systemic remediation.”
On August 10, 2017, Biocon had a teleconference with the USFDA to discuss the “questions/commitments requested” by the latter’s office of manufacturing quality (OMQ). On August 16, 2017, Kiran Mazumdar Shaw, chairperson and managing director (CMD), Biocon Limited, wrote to USFDA: “We have already proactively engaged qualified TPCs and will continue to bring on board additional external consultants/experts as needed to assist us in meeting the CGMP requirements for aseptic drug product manufacturing in a holistic and comprehensive manner.” She added that the company will engage qualified TPCs to assess the effectiveness of the corrective and preventive actions and evaluate its “quality systems and manufacturing operations” at the Bengaluru facility within six months.