Report Indicates Need for Greater Third Party Ingredients Certification to Ensure GMP Vigilance

CPhI Worldwide and CPhI Pharma Evolution, part of UBM Live’s Pharmaceutical portfolio, have announced the conclusions of the first monthly report into the current status of the formulation and ingredients market, conducted amongst high-level executives and experts from across the industry over the last month.

The report echoes concerns that the regulatory bodies (FDA, EMA) have raised with regards to the necessity of third party auditors to ensure the safety and quality of API and ingredient facilities. Nearly 95% of the respondents agreed that supplier’s certification was an important factor, yet despite this, only less than a quarter were actively working with third party auditors to vet suppliers, suggesting a greater vigilance is needed to a problem that the industry is still avoiding.

Of those working with third parties, nearly 31% of respondents said they are working with USP’s Verified Ingredients Program, with 18% using EXCIPACT and 10% using either IPEC or APIC.

The lack of action on the part of industry is owing to poor communication both internally and with suppliers according to Girish Malhotra, CPhI expert industry panel member. He said: “People who are visiting supplier sites must be familiar with manufacturing and analytical practices and both suppliers and buyers must agree on what certifications are needed. No shortcuts!”

Fellow panel members echoed these thoughts, with Brian Carlin commenting: “The combination of concerns over quality, supply and a lack of understanding suggest the need to move to more pharmaceutically aligned suppliers,” and Emil Ciurczak adding: “There are inconsistencies because we work in silos.”

In fact, half of the respondents felt quality was a top issue, with 41% adding that supply was a major issue with APIs and ingredients. However, problems with quality may not be entirely down to a lack of certification of ingredients according to Carlin: “If inconsistency of quality is due to unknown excipient attributes beyond the certification of analysis, part of the problem may be inadequate feedback to suppliers.”

Outsourcing is widely recognised as a major trend across the industry, yet despite this only just over a third of the industry is currently partnering with CMOs and CDMOs, which perhaps reflects a reluctance to outsource NCE development for fear of potential IP infringement. However, over half the respondents are already working with CROs during clinical trials and nearly 40% are currently working with academic groups during development.

The leading formulation issues, according to the survey respondents, are a result of new drug targets becoming more complex and suffering from solubility issues and poor release profiles. Over two thirds of the pharmaceutical sector suggested ‘bioavailability’ and ‘stability’ were pressing challenges for the industry today, with ‘dissolution’ and ‘release’ profile also being sources of major concerns for over half the industry.

Solid dosage forms of tablets and capsules still represent 70% of the market with particle size reduction (60%) and tabletting and compression (20%) seen as the most difficult to control operations. One solution to this problem could be an increased use of cross-functional teams, with 21% actively hiring and 35% planning to hire more material scientists.

“Material science is a good addition to the diverse range of expertise required for good QbD,” noted Carlin. Already the report highlights that PAT and QbD are being used more in formulation projects, with 35% saying they are using both and a further 36% planning to use them in the near future.

Yet despite these encouraging signs, Ciurczak is critical of the industries hesitance: “65% of the respondents are waiting to see if QbD really works … when the concepts have already been proven to work in every other industry in the world.” Carlin, on the other hand, has a more optimistic outlook, especially since the FDAs Office of Generic Drugs is encouraging the adoption of QbD: “The ANDA checklist in being updated to include elements of QbD and as such ANDAs will not be accepted for filing without these elements”.

The report concludes that overall the pharmaceutical API and ingredients market is becoming more global and competitive and as regulations change the overall business environment and drug manufacturers will have to adopt. Malhotra added: “Companies in the EU and the US have to work with their suppliers to emphasise the value of quality. Quality can no longer be taken for granted and a signed paper is no guarantee.”

As to the source of most APIs and ingredients, unsurprisingly over 45% answered India, followed by 25% for China and 19% for Europe. More interestingly however, 62% of respondents said they have focused their solid dose efforts onto extended release and orally disintegrating forms.    

CPhI Worldwide, cphi@ubm.com, Pharma Evolution, www.pharmaevolution.com.