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The report highlights a need for greater third party certification to ensure GMP vigilance.
CPhI Worldwide and CPhI Pharma Evolution, part of UBM Live’s pharmaceutical portfolio, has announced conclusions of the first monthly report. A survey on the current status of the formulations and ingredients market was conducted amongst high-level executives and experts from across the pharmaceutical industry during the last month.
The report echoes the concerns of regulatory bodies, such as FDA and EMA, regarding the necessity of third party auditors to ensure the safety and quality of API and ingredients facilities. While nearly 95% respondents agree that supplier’s certification is important, only less than a quarter are actively working with third party auditors to vet suppliers, suggesting that the industry is still avoiding the problem despite the need for greater vigilance.
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.
Girish Malhotra, CPhI expert industry panel member, attributes the industry’s lack of action to poor communication both internally and with suppliers. “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,” Malhotra said in a press release.
Fellow panel member, Brian Carlin, pointed out that “the combination of concerns over quality, supply, and a lack of understanding suggest the need to move to more pharmaceutically aligned suppliers.”
Quality was a top issue for 50% of respondents, with 41% adding that supply was a major issue with API and ingredients. Carlin, however, commented that problems with quality may not entirely be due to the lack of certification of ingredients. “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,” said Carlin.
It is well recognized that the pharmaceutical API and ingredients market is becoming more global and competitive. India and China are thriving as leading suppliers for APIs and ingredients, with 45% of respondents answering India as their source, followed by 25% for China, and 19% for Europe. However, changes in regulations mean that drug manufacturers will have to adapt their business strategies. “Companies in the EU and the US have to work with their suppliers to emphasize the value of quality. Quality can no longer be taken for granted and a signed paper is no guarantee,” said Malhotra.
The report notes that outsourcing is a major trend across the industry; however, there is still a reluctance to use CMOs and CDMOs when developing new chemical entities for fear of potential IP infringement. According to the report, only just over a third of the industry is partnering with CMOs and CDMOs. Despite this, more than half of the respondents indicated that they are already working with CROs during clinical trials and nearly 40% are currently collaborating with academic groups in research and development.
Bioavailability and stability remain as major obstacles in formulation as indicated by more than two thirds of respondents. With new drug targets becoming more complex, poor solubility and poor release are major concerns for more than half the pharmaceutical industry.
Solid dosage forms of tablets and capsules still represent 70% of the market. According to 62% of respondents, they have focused their solid dose efforts onto extended release and orally disintegrating forms.
The most difficult to control operations facing the industry are particle size reduction (60%) and tableting and compression (20%). 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,” stated Carlin. 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. However, panel member, Emil Ciurczak is critical about the hesitance within the industry and questions the “65% of respondents who are waiting to see if QbD really works when the concepts have already been proven to work in every other industry in the world, from cake mixers to cars.”
Carlin, on the other hand, has a more optimistic outlook, as 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.”
“This report has highlighted some really striking findings that both suppliers and pharma need to take account of, particularly in relation to quality and inspections, as it is impossible in a globalized environment to inspect every pharmaceutical ingredients plant on the planet- so independent certification is a must,” said Chris Kilbee, group director, CPhI & Pharma.
“Beyond this, it is clear that in terms of formulation for NCEs bioavailability and stability remain difficult to achieve with the proliferation of more complex drug compounds. And in fact, it is likely that as certification improves, pharma will increasingly look to outsource the development process and it is from this increased competition that solutions to formulation issues will be found. In the future, this will enable drug targets that were previously unworkable and reformulations of existing compounds to make it through the development cycle and on to commercial supply.”