From a regulatory standpoint, it is the sponsor which is held accountable if any contractor fails to comply to any GxP regulated activity, Amer Alghabban, Managing Director of consultancy firm GxP Compliance & Training Partners, reminded delegates at the Global Pharmaceutical Contract Manufacturing (GPCM) conference in London last month.
Therefore, compliance audits of third-party producers are essential to assure the quality of a product and ensure supply especially in qualification and selection of a partner, he continued. Furthermore, if carried out and used appropriately they can benefit a contract manufacturing organisation (CMO) as well by avoiding any unexpected surprises from regulatory inspections.
“For a CMO, an audit from a customer can pull up issues and discover gaps and non-conformities. However, a CMO can correct these and thus such an audit from a client is better than one from the regulators that results in a 483 or warning letter, as, at worst, it will lose one client rather than all,” Alghabban explained.
Furthermore, an audit allows a CMO to demonstrate abilities unknown to the sponsor and may lead to new contracts or a closer, strategic relationship, he said, citing his own experiences as Director of Quality Assurance and Auditing at Merck Serono,
Alghabban – who has also been on the other side of the auditing fence, having worked at the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) – continued to say that even CMOs who had received US FDA 483s or Warning Letters were far from being blacklisted by current or prospective pharma clients.
“Why wouldn’t [a sponsor] touch them again? If [the CMO] has done a wonderful CAPA on it and improved it, why go to someone who hasn’t experienced the problem yet,” he said, adding “we all make mistakes.”
Always show your working
An audit is one of the latter stages in commencing or renewing a contract with a CMO, and Alghabban also spoke about the initial stages of attempting to select a manufacturing partner from the thousands available. Unless requirements are rare or unique, thus immediately limiting production options, the challenge for the sponsor is completing a comprehensive and fully objective selection process.
Before filtering a list of potential CMOs down to an auditable number, a sponsor should have a list of anything up to 50 firms whittled down in a prescreening process incorporating information gathered from conventions, past experiences, and word of mouth, Alghabban said.
“Prescreening is essential,” he said, and “most companies either skip this part, as they say it takes time, or do it without actually documenting it.” However, he warned, if there is no documentation it has not been carried out, as far as the regulators are concerned.