Issue link: https://www.e-digitaleditions.com/i/377863
16 September 2014 Tablets & Capsules However, the guidance continues, "Depending on how the proposed change might affect product quality, addi- tional process design and process qualification activities could be warranted." An associated footnote further states, "Certain manufacturing changes may call for for- mal notification to the Agency before implementation." In reality, the SUPAC guidances do not address minor process changes within the operation of currently used equipment. It would be interesting to hear the FDA's view on that. Furthermore, it would be helpful if minor pro- cessing changes could be accepted by the FDA after they have undergone proper risk assessment and vetting by a company's quality management experts. Outside the USA, manufacturers may have more lati- tude; it depends on what they stated in the regulatory dossiers. But in general, outside the USA, actual batch manufacturing documents are not submitted to regulatory authorities, and minor changes to processes, so long as they are geared toward optimizing quality, are more acceptable. Thus improvements linked to grade substitu- tions or adjustments to operating conditions of the cur- rent equipment are less likely to concern regulators. Laboratory testing that evaluates process changes on small-scale equipment is also more likely to be accepted and have in fact been used to substantially improve yields and reduce batch failures. Conclusion More manufacturers are turning to lab-scale and at-line compression and fracture testing instruments to implement a continuous QbD approach to tablet development. We can thus look forward to significant improvements in tablet properties as these small-scale experiments identify better excipients and processes. This, in turn, will improve consis- tency and yield while reducing batch failures and costs, which are all benefits that ultimately accrue to patients. As an industry, our goal should be to convince the FDA to allow minor processing changes or grade substitutions within a pharmacopoeial specification. Such changes are in the best interests of both pharmaceutical manufacturers and patients because they improve existing products and reduce batch failures. In short, the FDA should give us the opportunity to implement a science-based, QbD ap - proach to tablet development using technology that con- tributes to a common goal: making better tablets. T&C References 1. Tablet Manufacture: Its History, Pharmacy and Practice. Wood JR. Page 3. JB Lipinott Company, 1906. 2. Tye CK, Sun CC, and Amidon GE. Evaluation of the effects of tableting speed on the relationships between compaction pressure, tablet tensile strength, and tablet solid fraction. J Pharm Sci 94 (3): 465-472 (2005). 3. The tensile strength of lactose tablets. Fell JR and Newton JM. J Pharm Pharmacol 20(8): 657-659 (1968). 4. Compression prediction accuracy from small scale compaction studies to production presses. Pitt KG et al. Powder Technology, in press. See: www.sciencedirect.com/ science/article/pii/S0032591013006104. 5. GTP-1 benchtop tablet press and material tester from Gamlen Tableting, Nottingham, UK. 6. Wood, ibid, page 4. 7. Determination of the tensile strength of elongated tablets. Pitt KG and Heasley MG, Powder Technology 238: 169-175 (2013). 8. Improved drug salt selection using an instrumented laboratory tablet press, Gamlen MJ et al., AAPS poster AM-13-3547 (2013). 9. Characterization of the compression properties of compacted chitosan as a function of molecular weight. Gamlen MJ and Rashid IS. AAPS poster AM-13-2015 (2013). 10. Measurement of tablet detachment and ejection forces using an instrumented laboratory tablet press. Gamlen MJ and Dey D. AAPS poster AM-13-2014 (2013). 11. "Guidance for Industry: Process Validation Guid - ance: General Principles and Practices." US FDA. www.fda.gov/downloads/Drugs/Guidances/UCM070336. pdf. January 2011, Washington, DC. Michael Gamlen, PhD, is managing director of Gamlen Tablet- ing, Biocity Nottingham, Nottingham NG1 1GF United Kingdom. Tel. +44 115 912 4271. Website: www.gamlen tableting.com. He has more than 30 years' experience in tablet development and led tablet development at The Wellcome Foun- dation for 15 years. He specializes in managing product devel- opment, formulation, and tablet and process development studies. Joe Domingue is president of SciMark International, Laguna Niguel, CA. Tel. 949 495 7795. E-mail: joe.domingue@ gmail.com. SciMark is the North American representative of Gamlen Tableting. Meet T&C staff Booth 3318 at AAPS in San Diego