LEGAL UPDATES BY BEPARTNERS
Health & Pharmaceuticals
BPOM Introduces Legal Framework for Human Cell-Based Medicine
18 September 2020

Human cell-based medicine is a widely practiced form of medicine for the past few decades, which has also been internationally practiced since 1978. In fact, the Indonesian government has also appointed 11 hospitals throughout Indonesia to engage in medical services using human cell-based medicine.[1] Throughout the years, the human cell-based medicine has experienced vigorous developments as it is believed that this medicine is able to cure many hard-to-cure diseases (unmet medical needs), such as diabetes, cancer, kidney failure and, given the relevant circumstances, may possibly even develop a  successful Corona Virus Disease 2019 (“Covid-19”) vaccine.

 

Human cell-based medicine is viewed as medicines developed from the human body’s somatic cell and/or product of human’s tissue engineering.[2] Because of the source of this medicine, human cell-based medicines has its own unique characteristic for each human, and even though this may come with many advantages, this may also incur higher stakes risks that vary throughout every human cell-based medicine produced from each human. These risks make human cell-based medicine different from usual basic medicines and therefore, the assessment for human cell-based medicine cannot be justified with the usual assessment for non-human cell-based medicines.

 

Given the current Covid-19 pandemic, scientists in Indonesia are continuing to develop human cell-based medicine as alternative medicines to treat Covid-19 patients. This has in turn brought up the urgency for government institutions to establish a plausible legal framework in the assessment and procedure on human cell-based medicine. The purpose of establishing such would ensure strong grounds of adherence in this particular area of medicine, where there will be clear guidelines for the following below parties in conducting their respective roles in human cell-based medicine:[3]

 

  1. evaluation and/or assessment of Cell-Based Medicines by evaluators;
  2. compliance with requirements for the registration of Cell-Based Medicines by registrars (i.e., pharmaceutical industries that have obtain pharmaceutical industry license[4]); and
  3. development of Cell-Based Medicines by research organizations.

 

Which regulation does the legal framework refer to?

 

The National Agency of Drug and Food Control’s (Badan Pengawas Obat dan Makanan – BPOM”) duty and function are regulators on monitoring the medicines circulated around Indonesia and possesses the responsibility to ensure that the human cell-based medicines used by the public are in good quality, safe and efficacious in this regulation. In light of such, on 20 July 2020, BPOM enacted BPOM Regulation No. 18 of 2020 on Guidelines on Assessment for Human Cell-Based Medicine (“BPOM Regulation 18/2020”).

 

Key Provisions

 

The purposes of the guidelines stipulated under BPOM Regulation 18/2020 are: (i) to provide guidelines on the requirements for human cell-based medicine registration in Indonesia; and (ii) to give guidelines on the evaluation of such human cell-based medicine.[5] These purposes are intended to become the basis for research institutions or industries and BPOM itself in regards to the granting/issuance of human cell-based medicine distribution permits.[6]

 

  1. Scope of the Guidelines

 

These guidelines apply to human cell-based medicine that is massively produced, where these guidelines are to be satisfied by the research organization and the registrars are obliged to obtain a human cell-based medicine distribution permit. These guidelines do not apply to the derivative products which are created from that human cell-based permit, autologous stem cell products and embryonic, or even blood product.[7] Nonetheless, certain parts of these guidelines still provide minimum requirements for stem cell manufacturing process.[8]

 

 2. Technical Requirements

 

These guidelines accommodate technical requirements, which consist of the following:[9]

 

  1. Risks Analysis

 

Risk analysis for human cell-based medicine should be done twice, which are briefly explained as follows:

 

  1. Initial risk analysis, conducted based on the knowledge of the particular human cell-based medicine and the purposes of the medicine itself. This should be performed and renewed constantly throughout the life cycle of the product as continuing data to indicate and the risks that may incur;
  2. Comprehensive risk analysis, is carried for the purpose of justification for product development and as the basis to prepare a risk management plan according to the applicable Guidelines on Risk Management Plan.

                          

  1. Quality Aspect and Manufacturing Process

 

The production of human cell-based medicine must be consistent with the principle of Good Drug Manufacturing Practice (Cara Pembuatan Obat yang Baik, “CPOB”). The compliance for CPOB is proved by the issuance of the CPOB certificate. Below are the requirements for human cell-based in regards to quality check and manufacturing process requirements:

 

 

3. Non-clinical Development

 

Non-clinical development must be carried out in accordance with the applicable guidelines on gene transfer, such as EMA Note for Guidance on the Quality, Preclinical and Clinical Aspects of Gene Transfer Medical Products (CMP/BWP/3088/99) and BPOM Regulation No. 24 of 2017 on Criteria and Procedure for the Registration of Medicines. The purposes of non-clinical studies are to prove the principles of the human cell-based medicine and to provide an explanation on the estimation of the pharmacological and toxicological effects of the human cell-based medicine towards the patient’s response of the human cell-based medicine. Other targets of the studies are to:[22]

 

  1. Choice of doses that is safe with respect to clinical test;
  2. Route and schedule for the distribution of human cell-based medicine;
  3. Duration of exposures and estimated time to follow up in regards to note the side effects of human cell-based medicine;
  4. Identification of toxicity level on the relevant targeted organs; and
  5. Identification of parameters to observe the patients who receive human cell-based medication.

 

 4. Clinic Development

 

Similar to other types of medicines, human cell-based medicine must go through clinical studies development. These clinical studies include the pharmacodynamics phase, pharmacokinetic phase, determination on work mechanism, determination on the dose for human cell-based medicine intake and irregular clinical studies according to the applicable Guidelines on Good Clinical Examination Practice in Indonesia (Pedoman Cara Uji Klinik yang Baik - CUKB”).[23]

 

5. Pharmacovigilance[24] and Risk Management Plan

 

Regular Pharmacovigilance and traceability of a new product are required to be inserted into the Risk Management Plan. Long term studies may be necessary for human cell-based medicine in order to supervise some specific safety issues, including potential/efficacy degradation. The Supervision for human cell-based medicine safety must be conducted consistently with BPOM Regulation No 3 of 2011 on the Implementation of Pharmacovigilance Performed by the Pharmaceutical Industry (“BPOM Regulation 3/2011”).[25]

 

Conclusion

 

According to a statement by Muhammad Dimyati, Director General of Research and Development Enforcement at the Ministry of Research, Technology and Higher Education, there are numerous policies established by the Government that is aiming to encourage the growth of downstream products wherein one of which includes the encouragement of human cell-based medicine products.  Although this regulation might not cover all parts and details of the process of human cell-based manufacturing, this regulation provides as a major breakthrough for Indonesian medicines. Bearing in mind that this medicine has a great ability to satisfy unmet medical needs, including the possibility to treat Covid-19. It is hoped that this regulation may provide comprehensive and applicable guidelines for human cell-based producer/businessmen and BPOM evaluators in regards to registration and examination of human cell-based medicine.

 

If there are any queries with regards to how this may affect your business, please contact us for further legal consultation.

 

This information does not, and is not intended to, constitute as legal advice; instead, all information, content, and materials are for general information only.

 

 

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[1] Minister of Health Decree No. 32/MENKES/SK/II/2014 on Stipulation of Hospitals as Medical Service, Research and Education Development Center for Tissue Bank and Stem Cells.

[2] Pursuant to Article 1 Number 2 of National Agency of Drug and Food Control (Badan Pengawas Obat dan Makanan – BPOM) Regulation No. 18 of 2020 on Guidelines on Assessment for Human Cell-Based Medicine (“BPOM Regulation 18/2020”).

[3] Pursuant to Article 2 Paragraph 1 of BPOM Regulation 18/2020.

[4] Ibid., Article 1 Number 3.

[5] Ibid., Page 9 of Chapter I of the Appendix.

[6] Ibid., Page 8

[7] Ibid., Page 9.

[8] The minimum requirement that must be satisfied are in regards to:

  1. the quality and manufacturing process of the stem cell (as set forth under Page 12-13 and 17 of Chapter II of the Appendix of BPOM Regulation 18/2020);
  2. characterization of the stem cell, which includes the identity, pollutant and tumorgenicity level of stem cell (as set forth under Page 22, 24, 28 and 29 of Chapter II of the Appendix of BPOM Regulation 18/2020);
  3. non-clinical development for stem cell in terms of its toxicity, preliminary pharmacodynamic, biodistribution studies (as set forth under Page 39, 40, 41 and 44 of Chapter II of the Appendix of BPOM Regulation 18/2020); and
  4. clinical development for stem cells in terms of its pharmacodynamic, pharmacokinetic, clinic efficacy and clinic safety (as set forth under Page 46-50 of Chapter II of the Appendix of BPOM Regulation 18/2020).

[9] Ibid., Page 10.

[10] Pursuant to Page 12 of Chapter II of the Appendix of BPOM Regulation 18/2020.

[11] Ibid., Page 14

[12] Ibid., Page 18-20

[13] Ibid., Page 22-29

[14] Ibid., Page 21

[15] Batch or bets in Indonesian language, means a number of medicines having the same characteristic and quality, producing from the same manufacturing cycle or under the specified manufacturing order.

[16] Pursuant to Page 29-30 of Chapter II of the Appendix of BPOM Regulation 18/2020.

[17] Ibid., Page 31.

[18] Ibid., Page 31-32.

[19] Ibid., Page 32.

[20] Ibid., Page 36.

[21] Ibid., Page 37.

[22]  Ibid.

[23] Ibid., Page 44; The applicable CKUB is the Third Edition of CKUB established in 2016.

[24] Pharmacovigilance, as set forth under Article 1 of BPOM Regulation No 3/2011, means all activities implemented in regards to detection, assessment, understanding and prevention on the side effects and other problems that might be caused by the consumption of certain medication.

[25] Pursuant to Page 50-51 of Chapter II of the Appendix of BPOM Regulation 18/2020.

 

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