Drugs are marketed only after their approval by regulatory authority. Only safe, effective and medicines of quality are approved by the regulatory bodies. This is what makes the approval process of a drug essential. Different regions have different regulatory authority. Even though for each regulatory body, the common goal is to provide safe and effective medicines, there are variations in process for drug approvals for regulatory bodies.
Read below to know more about the global drug approval process.
Key Regulatory Authorities Drug Approvals
US FDA Drug Approval Process
Discovery and Development: Number of molecular compounds are potential candidates to develop into a new drug. After initial testing, only a small fraction of them is eligible for further studies. Then they start to work to develop the drug i.e. to gather more information regarding the pharmacokinetic and pharmacodynamic properties.
Preclinical Studies: After a promising molecule has been found, it will be then tested in animals prior to its testing in humans. This is one to find whether the molecule is capable of causing any serious harm. Researchers must follow GLP (Good Laboratory Practice) guidelines. Detailed information on the doing and the toxicity of the molecule must be obtained via this study.
Clinical Studies: After preclinical testing, the researchers will decide whether to test the substance in humans or not based on the information in hand. Clinical research is conducted to know how the drug behaves in the human body, its safety and effectiveness. To begin the research, an IND (Investigational New Drug) application must be submitted to the FDA. Clinical trials follow a series, from phase 1 (Early, small-scaled study) to phase 3 (Late, large-scaled study).
FDA Review: Once enough evidence on the safety and effectiveness of the drug is generated from the preclinical and clinical research, an application can be submitted to market the drug. This is the New Drug Application (NDA). If the NDA is complete, then the FDA has 6 to 10 months to decide whether to approve the application to market the drug.
EMA Drug Approval Process
Research and Development: Only a small number of molecules are promising for further studies in patients. This is the same for every drug development process. These molecules are tested in the laboratory and then in humans, the clinical trials. Drug developers who plan to conduct clinical trials in the EU should submit applications. Applications are submitted to the national competent authorities of the countries in which they want to conduct the trials.
Scientific Advice: For a medicine to be marketed, the drug developers have to demonstrate that it is safe, effective and is of quality. During the development process of a drug, the developer can request the EMA for any guidance or direction on the best methods/ study designs. This can help in generating robust information on how well and safe a medicine can be. This is known as scientific advice.
Evaluation: To acquire marketing authorization, specific data on the drug must be submitted by the drug developer. The EMA conducts a thorough assessment and determines whether the supposed drug is safe and effective for its intended use. For about 6 - 7 months prior to the application submission, the drug developers can have a meeting with the EMA and make sure that their application satisfies all the legal and regulatory requirements. This allows for increased application quality and decreased approval delays.
Authorization: A drug is authorized only if the benefit of the drug outweighs its risks. The EMA makes a recommendation to the European Commission which then takes a final decision on whether or not the drug can be marketed in the EU. This is issued within 67 days of receival of EMA’s recommendation. For all centrally authorized products, the commission is the authorizing body.
PMDA Drug Approval System
Here is the drug approval process of Pharmaceuticals and Medical Devices Agency.
Research and Development: This step is similar to every drug development process. Once a molecule worthy enough to be a new drug is found, the next stage of drug development is started.
Non-Clinical Tests: Nonclinical or preclinical tests are performed. Laboratory tests are also performed. This is done to identify any potential risks that can be a threat to humankind. The safety, efficacy and pharmacological properties are also assessed.
Clinical Trials: Once the molecule has passed this phase, an IND is applied to begin the clinical trials of the molecule/drug. An IND application must be submitted in the CTD format to the PMDA. Once the IND is submitted with all the required information, the PMDA reviews and forwards it to the IRB. After the approval of IRB clinical trials can be conducted. Clinical trials are conducted in 3 phases. Phase1, Phase 2 and Phase 3.
Filling of Application: After quality, safety and efficacy data are generated on the drug, the applicant must file for an NDA application. This is submitted to PMDA to gain market approval.
Approval: The PMDA review team with various scientific field specialists will review the application. They also exchange opinions with external experts. The review team prepares a review report and submits it to MHLW (Ministry of Health, Labor and Welfare). The MHLW then seek advice from the Pharmaceutical Affairs Council and decide on the approval of the drug.
TGA Pathway For Drug Approval
TGA has 3 pathways that can be used to assess prescription medicine. They are 1) The Standard Pathway, 2) The Priority Review Pathway, 3) Provisional Approval Pathway. The priority review and provisional approval pathways are used to make the drugs available in the market sooner than the standard process. Drugs that are for serious or life-threatening conditions. The following is the process for most of the applications:
Pre-submission: Prior to an application submission, the sponsors must verify that the product meets all the eligibility requirements for the pathway of assessed listed medicines. Correct determination of the application category is important. If the category is confused and the application does not meet the requirements and required data is lacking, then it won't be accepted for evaluation. Applicants can have a pre-submission meeting with TGA to address any questions.
Submission: For the listing and registration of medicines on ARTG (Australian Register of Therapeutic Goods), the business service portal of the TGA provides an electronic facility. If the submission of the application has been done, a unique submission number will be given to the applicant.
Preliminary Assessment: A preliminary assessment will be conducted by TGA so as to decide whether the application has all the requirements needed to proceed evaluation.
Evaluation and requests for information: If preliminary assessment is completed and the evaluation fee has been paid, evaluation starts. TGA will evaluate the product and can request additional information. This happens when there is any clarification needed or to address issues that are found at this time. TGA can also take advice from an expert advisory committee.
Decision: The Delegate of the Secretary of the Department of Health is the decision maker and decides whether to list the drug in the ARTG (Australian Register of Therapeutic Goods). All the relevant documents linked to the application are reviewed. Dossier, reports of evaluation, requests for information responses, guidance from expert advisory committee are reviewed as well.
Finalization: A patent certificate should be provided by the sponsor or notification that it is not needed before listing the drug in ARTG. Upon receival of the completed and signed notification form or patent certificate, medicine is listed in ARTG. A unique AUST L(A) number is given for the product.
Post-listing: The TGA can choose to publish a notification on the TGA website regarding the approval of the medicine.
CDSCO Drug Approval Process
In India, The Drug Controller General of India (DCGI, which is under CDSCO) regulates the clinical trials. After the researchers have managed to gather enough information on the drug from preclinical studies, clinical trials are conducted. An application must be submitted to conduct a clinical trial. Clinical trials are conducted in 3 phases.
After the completion of clinical trials and evidence on safety and efficacy are gathered, an application for new drug approval must be submitted to CDSCO.
Applicant must submit an application on Form 44 to CDSCO together with the fee. The application is verified for its completeness of the data and requirements. If any deficiencies are found, a deficiency letter is sent to the applicant.
The chemistry, manufacturing and controls (CMC) data are reviewed. If all the CMC data are satisfactory then the application moves to the next step.
If a BE (Bioequivalence) study is necessary or is required by the CDSCO, the permission to conduct the study is granted to the applicant in the form of NOC. When the study is completed and the reports are submitted, the CDSCO reviews these reports as well.
An IPC NOC is provided after the review of the CMC data. This indicates that the drug is in compliance with the IPC (Indian Pharmacopoeia Commission) specified quality standards.
An inspection can be conducted if deemed necessary. Relevant site inspection can be conducted if there arises any query or clarification to make sure regulatory standard compliance.
After completion of review and other steps the final approval is given.
FDA Acceptance Of Foreign Clinical Data
FDA will accept foreign clinical studies as support for marketing applications under certain conditions. The conditions include:
Clinical studies must follow GCP guidelines. It also requires informed consent from subjects as well as review and approval by IEC.
Foreign data must be applicable to the US population and medical practice.
The studies performed by the clinical investigators must have recognized competence.
FDA will consider the data valid without an onsite inspection but, if necessary, the FDA can also validate the data through onsite monitoring.
The applicants are advised to have a consultation with the FDA officials in the pre submission meeting.
Supporting information, waivers and records stated in 21 CFR part 312.120.
Tips To Speed Up Drug Development Approvals
Although the drug development and approval are a lengthy and time-consuming process, it can be driven a bit faster than the existing ones. Some key tips to be noted are: -
Make use of the accelerated drug approval procedures, the fastrack approval pathways.
Early and effective communication with the regulatory authority officials.
Follow GLP, GCP and GMP standards.
Search for and get help from all the new technologies and professionals that allow for an expedited drug development pathway.
Submission of all the required data and timely response to the queries raised by the authorities.
Proper designing of the clinical trials helps in gathering accurate data which allows for accelerated drug approval procedures.
Outsourcing some aspects can help to decrease the R&D cost. It also presents an opportunity to use expert advice/guidance in the regulatory field. Artixio Consulting provides services on global market access and regulatory compliance for drugs, medical devices, cosmetics and more. Our team of experts in various regions assures you of a streamlined regulatory approval process. Connect with us on info@artixio.com
FAQs
Q. Who regulates pharmaceutical approvals globally?
A. Globally, pharmaceuticals are approved by national and regional regulatory bodies of the respective regions in which they wish to market the drug. For example, FDA for the US, TGA for Australia, Health Canada for Canada and so on.
Q. How do MRAs benefit pharmaceutical companies?
A. It provides for quicker market access by streamlining the approval and reducing duplication. Improved access of patients to medicines, decreased uncertainty in the regulatory processes, cost reduction, speeding up in the manufacturing and distribution process are some of the other benefits for pharmaceutical companies.
Q. What’s the fastest drug approval pathway in the U.S. and EU?
A. In the US the fastest drug approval pathways are priority review, accelerated approval program and the fast track program. For the EU, the pathways for faster drug approval include conditional marketing authorization (CMA) and PRIME (Priority Medicines).
Q. Why is regulatory harmonization important?
A. Regulatory harmonization is essential as it leads in upgrading the efficiency in the regulatory review processes. Another factor is that it decreases the time consumption to make a product available in the market. It favors patient burden reduction by preventing unnecessary duplication of clinical trials and post market clinical evaluations. It also plays a role in reducing unnecessary animal testing without compromising safety and effectiveness.
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