- Particle size reduction a major challenge for 60% industry during formulation
- Bioavailability still a major formulation obstacle- with two thirds listing it as their most urgent challenge
- India and China thriving as leading API source
- However quality is still seen as the top issue with APIs and ingredients for half of the industry
- Over half of respondents outsource clinical work to CROs
- There is still a reluctance to use CMOs and CDMOs when developing new chemical entities
- Academic partnerships are on the rise with nearly 40% working with them
CPhI Worldwide and CPhI Pharma Evolution, part of UBM Live’s Pharmaceutical Portfolio, announce the conclusions of its 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 the regulatory bodies (FDA, EMA) have raised in regards to the necessity of third party auditors to ensure the safety and quality of API and ingredients 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 due to poor communication both internally and with suppliers according to Girish Malhotra, CPhI expert industry panel member. “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 Emil Ciurczak, commenting “there are inconsistencies because we work in silos”, whilst Brian Carlin reiterated these sentiments adding “the combination of concerns over quality, supply and a lack of understanding suggest the need to move to more pharmaceutically aligned suppliers”.
In fact, half of the respondents felt quality was a top issue, with 41% adding that supply was a major issue with API 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 new chemical entity 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 tableting 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” notes Carlin. Already we are seeing 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 “so 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, from cake mixers to cars”. However, Carlin 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. “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” added Malhotra.
As to the source of most APIs and ingredients unsurprisingly over 45% answered India followed by 25% for China and 19% for Europe as the top supplier. More interestingly however, 62% of respondents said they have focused their solid dose efforts onto extended release and orally disintegrating forms.
Chris Kilbee - Group Director, CPhI & Pharma - commenting on the success of CPhI’s first monthly insight report: “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 globalised environment to inspect every pharmaceutical ingredients plant on the planet- so independent certification is a must. 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”.