FDA Regulatory Implications for Co-crystals and recent Co-crystal Patents

  • Samuel Rigilin Department of Pharmaceutics, Srinivas College of Pharmacy, Valachil, Mangalore, Karnataka, India – 574143
  • Krishnananda Kamath Kunjal
  • Abdul Raheem Thayyil
  • Ramakrishna Shabaraya

Abstract

One of the most crucial stages in the creation of a medicinal product is the characterization of an Active Pharmaceutical Ingredient (API). Unfortunately, not all APIs have the ideal characteristics for medicinal usage. Many freshly discovered active compounds, for example, have low solubility. However, various methods have been developed to change and improve an API's features to get desired physicochemical properties, which is an important tool in formulation development. The production of salt derivatives is a common technique for increasing the solubility of an active chemical. This method, however, has limits because not every API has the qualities to be transformed into a salt. In recent years, a novel engineering approach for creating new API forms with desirable features has been established. The development of pharmaceutical co-crystals is the result of these efforts which allow pharmaceutical companies to customise existing APIs or create new ones with specific properties. Aside from the scientific hurdles that come with developing a pharmaceutical, manufacturers are also faced with regulatory regulations that must be met in order to get approval and access the market. As pharmaceutical co-crystals are a relatively new API, little regulatory guidance for co-crystals has been developed for one of the world's largest pharmaceutical market the United States of America (USA).


This article will look at what regulatory standards must be met in order to employ pharmaceutical co-crystals in generic medications intended for use in the United States. It will also go over which data should be included in the common technical document to justify its existence. In addition to, a brief information of various patents on co-crystals have also been included for better knowledge of the reader.

Keywords: Pharmaceutical co-crystals, Coformer, Regulatory guidelines, Common technical document, FDA, Patent

Downloads

Download data is not yet available.

References

1. Schultheiss N, Newman A. Pharmaceutical co-crystals and their physicochemical properties. Cryst. Growth Des. 2009 Jun 3;9(6):2950-67.
2. Thimmasetty J, Ghosh T, Nayak NS, Raheem A. Oral Bioavailability Enhancement of Paliperidone by the use of Cocrystalization and Precipitation Inhibition. J. Pharm. Innov. 2021 Mar;16(1):160-9.
3. Greenwood NN, Earnshaw A. Chemistry of the Elements.2nd edition. Elsevier; 1997
4. Boothroyd S, Kerridge A, Broo A, Buttar D, Anwar J. Why do some molecules form hydrates or solvates? Cryst. Growth Des. 2018 Feb 5;18(3):1903-8.
5. Stahly GP. Diversity in single-and multiple-component crystals. The search for and prevalence of polymorphs and co-crystals. Cryst. Growth Des. 2007 Jun 6;7(6):1007-26.
6. Bhogala BR, Nangia A. Ternary and quaternary co-crystals of 1, 3-cis, 5-cis-cyclohexanetricarboxylic acid and 4, 4′-bipyridines. NJC. 2008;32(5):800-7.
7. Childs SL, Hardcastle KI. Co-crystals of piroxicam with carboxylic acids. Cryst. Growth Des. 2007 Jul 3;7(7):1291-304.
8. Vishweshwar P, McMahon JA, Bis JA, Zaworotko MJ. Pharmaceutical co-crystals. J. Pharm. Sci. 2006 Mar 1;95(3):499-516.
9. Bond AD. What is a co-crystal? CrystEngComm. 2007;9(9):833-4.
10. Jones W, Motherwell WS, Trask AV. Pharmaceutical co-crystals: An emerging approach to physical property enhancement. MRS bull. 2006 Nov;31(11):875-9.
11. Aakeröy CB, Salmon DJ. Building co-crystals with molecular sense and supramolecular sensibility. CrystEngComm. 2005 Jul 4; 7:439-48.
12. US Food and Drug Administration. Guidance for industry: Regulatory classification of pharmaceutical co-crystals [Internet]. US: Center for Drug Evaluation and Research, Silver Spring; 2013 Apr. [cited 2022 Jun 03]. Available from:
https://www.fda.gov/files/drugs/published/Regulatory-Classification-of-Pharmaceutical-Co-Crystals.pdf
13. Aitipamula S, Banerjee R, Bansal AK, Biradha K, Cheney ML, Choudhury AR, Desiraju GR, Dikundwar AG, Dubey R, Duggirala N, Ghogale PP. Polymorphs, salts, and co-crystals: what’s in a name? Cryst. Growth Des. 2012 May 2;12(5):2147-52.
14. FDA to Reclassify Pharmaceutical CoCrystal [Internet]. Regulatory Affairs Professional Society;2016 [cited 2022 Jun 4]. Available from:
https://www.raps.org/regulatory-focus%E2%84%A2/news-articles/2016/8/fda-to-reclassify-pharmaceutical-co-crystals
15. Guidance for Industry Regulatory Classification of Pharmaceutical Co-Crystals [Internet]. FDA; 2018 [cited 2022 Jun 4]. Available from:
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/regulatory-classification-pharmaceutical-co-crystals
16. Boehm G, Yao L, Han L, Zheng Q. Development of the generic drug industry in the US after the Hatch-Waxman Act of 1984. APSB. 2013 Sep 1;3(5):297-311.
17. Guidance for Industry ANDAs: Pharmaceutical Solid Polymorphism [Internet]. FDA; 2007, July 10 [cited 2022 Jun 3]. Available from:
https: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/andaspharmaceutical-solid-polymorphism-chemistry-manufacturing-and-controls-information
18. Guideline IH. Organisation of the Common Technical Document for the Registration of Pharmaceuticals for Human Use M4 [Internet] Geneva:ICH; 2004 [cited 2022 Jun 3] Available from:
https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-m4-r4-common-technical-document-ctd-registration-pharmaceuticals-human-use_en.pdf
19. Cruz-Cabeza AJ. Acid–base crystalline complexes and the p K a rule. CrystEngComm. 2012;14(20):6362-5.
20. Borg JJ, Robert JL, Wade G, Aislaitner G, Pirozynski M, Abadie E, Salmonson T, Bonanno PV. Where is industry getting it wrong? A review of quality concerns raised at day 120 by the Committee for Medicinal Products for Human Use during European Centralised Marketing Authorisation Submissions for chemical entity medicinal products. J. Pharm.Pharm.Sci. 2009 Aug 7;12(2):181-98.
21. Food and Drug Administration. Guidance for Industry Nonclinical Studies for the Safety Evaluation of Pharmaceutical Excipients [Internet]. FDA; 2005 May 12 [cited 2022 Jun 03]. Available from:
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/nonclinical-studies-safety-evaluation-pharmaceutical-excipients
22. Guidance for Industry Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA [Internet]. FDA; 2013 [Cited 2022 Jun 03]. Available from:
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bioequivalence-studies-pharmacokinetic-endpoints-drugs-submitted-under-abbreviated-new-drug
23. Guideline on the Investigation of Bioequivalence [Internet]. 2010 [cited 2022 Jun 03]. Available from:
https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-investigation-bioequivalence-rev1_en.pdf
24. Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System [Internet]. FDA; 2017 [cited 2022 Jun 03]. Available from:
https://www.federalregister.gov/documents/2017/12/26/2017-27786/waiver-of-in-vivo-bioavailability-and-bioequivalence-studies-for-immediate-release-solid-oral-dosage
25. Davit BM, Kanfer I, Tsang YC, Cardot JM. BCS biowaivers: similarities and differences among EMA, FDA, and WHO requirements. The AAPS journal. 2016 May;18(3):612-8.
26. Raheem Thayyil A, Juturu T, Nayak S, Kamath S. Pharmaceutical Co-Crystallization: Regulatory Aspects, Design, Characterization, and Applications. Adv Pharm Bull. 2020 Jun;10(2):203-212.
27. Kumar A, Kumar S, Nanda A. A review about regulatory status and recent patents of pharmaceutical co-crystals. Adv. Pharm. Bull. 2018 Aug;8(3):355.
28. Fala L. Entresto (Sacubitril/Valsartan): first-in-class angiotensin receptor neprilysin inhibitor FDA approved for patients with heart failure. Am. Health Drug Benefits. 2015 Sep;8(6):330.
29. Harrison WT, Yathirajan HS, Bindya S, Anilkumar HG. Escitalopram oxalate: co-existence of oxalate dianions and oxalic acid molecules in the same crystal. Acta Crystallogr.2007 Feb 15;63(2): o129-31.
30. Mascitti V, Thuma BA, Smith AC, Robinson RP, Brandt T, Kalgutkar AS, Maurer TS, Samas B, Sharma R. On the importance of synthetic organic chemistry in drug discovery: reflections on the discovery of antidiabetic agent ertugliflozin. MedChemComm. 2013;4(1):101-11.
31. Poole RM, Dungo RT. Ipragliflozin: first global approval. Drugs. 2014 Apr;74(5):611-7.
32. Chavan RB, Thipparaboina R, Yadav B, Shastri NR. Continuous manufacturing of co-crystals: challenges and prospects. Drug Deliv. Transl. Res. 2018 Dec;8(6):1726-39.
33. Devarakonda SN, Vyas K, Bommareddy SR, Padi PR, Raghupathy B, inventors; Reddys Laboratories Ltd, Reddys Laboratories Inc, assignee. Aripiprazole co-crystals. United States patent application US 12/278,022 [Internet]. US: United States patent application ; 2009 Feb 26[cited 2022 Jun 03]. Available from:
https://patents.google.com/patent/EP1988899A4/en
34. freshpatents.com [Internet]. Fresh Patents; 15 Feb 2018 [cited 2022 Jun 03]. Available from:
http://www.freshpatents.com/- dt20111020ptan20110257215.php
35. Almarsson Ö, Peterson ML, Zaworotko M. The A to Z of pharmaceutical co-crystals: a decade of fast-moving new science and patents. Pharm. Pat. Anal. 2012 Jul;1(3):313-27.
36. Smith AJ, Kim SH, Duggirala NK, Jin J, Wojtas L, Ehrhart J, Giunta B, Tan J, Zaworotko MJ, Shytle RD. Improving lithium therapeutics by crystal engineering of novel ionic co-crystals. Mol. Pharm. 2013 Dec 2;10(12):4728-38.
37. Ong TT, Kavuru P, Nguyen T, Cantwell R, Wojtas Ł, Zaworotko MJ. 2: 1 Co-crystals of homochiral and achiral amino acid zwitterions with Li+ salts: water-stable zeolitic and diamondoid metal–organic materials. J. Am. Chem.Soc. 2011 Jun 22;133(24):9224-7.
38. Dandela R, Reddy JS, Viswanadha GS, Nagalapalli R, Solomon AK, Gaddamanugu G, et al. Novel co-crystals/molecular salts of mesalamine to be used as improved anti-inflammatory drug. WO Patent 2012090224A1 [Internet]. Nutracryst Therapeutics Private Limited; 2010 [cited 2022 Jun 3]. Available from:
https://patents.google.com/patent/WO2012090224A1/en
39. Reddy JS, Dandela R, Viswanadha GS, Nagalapalli R, Solomon AK, Javed I, et al. Novel co-crystals / molecular salts of metformin with oleoylethanolamide as an effective anti-diabetic + anti- obesity agent. WO Patent 2012090225A2 [Internet]. Nutracryst Therapeutics Private Limited; 2010 [cited 2022 Jun 3]. Available from:
https://patents.google.com/patent/WO2012090225A2/en
40. Kumar A, Nanda A. Ever-greening in pharmaceuticals: strategies, consequences and provisions for prevention in USA, EU, India and other countries. Kumar A, Nanda A, Ever-greening in Pharmaceuticals: Strategies, Consequences and Provisions for Prevention in USA, EU, India and Other Countries. Pharm Regul Aff. 2017 Mar 5; 6:185.
Statistics
183 Views | 220 Downloads
How to Cite
Samuel Rigilin, K. K. Kunjal, A. R. Thayyil, and R. Shabaraya. “FDA Regulatory Implications for Co-Crystals and Recent Co-Crystal Patents”. International Journal of Drug Regulatory Affairs, Vol. 10, no. 3, Sept. 2022, pp. 10-18, doi:10.22270/ijdra.v10i3.541.