[Updated] China Pharma Guidelines: Nonclinical Study, Clinical Trial, Marketing Authorization and More

China has been actively releasing pharmaceutical guidelines to provide guidance to the industry throughout various stages of a drug's lifecycle, including nonclinical studies, clinical trials, marketing authorization applications, pharmacovigilance, and more.

The guidelines are mainly issued by the National Medical Products Administration (NMPA) and the Center for Drug Evaluation (CDE), which is NMPA’s office for accepting and reviewing drug registration applications.

Adhering to these guidelines is crucial as it helps streamline the drug evaluation process, significantly reducing the likelihood of receiving deficiency letters or facing disapproval from regulatory authorities. By following these guidelines, companies can enhance their chances of successful drug approvals and expedite their entry into the Chinese market.

The draft guidelines also offer valuable insights into the perspectives and considerations of Chinese drug regulators on specific issues. During the consultation period, companies are encouraged to provide comments and advice on the drafts. By analyzing draft guidelines, companies can proactively adapt to the evolving regulatory landscape and promptly meet future requirements.

To facilitate access to the guidelines, BaiPharm has collected the latest guidelines on chemical drugs, biologics, and traditional Chinese medicines (TCMs). This collection will be expanded and updated on a weekly basis, ensuring industry stakeholders remain up to date with the latest regulatory updates from China.

Nonclinical Research

No	Guidelines	Authority	Status	Issued	Enforced
1	Technical Guidelines on Nonclinical Studies on Antibody Drug Conjugates (ADCs)	CDE	Draft	27/09/2023	/
2	Guidelines on Nonclinical Studies on Enzyme Replacement Therapies for Rare Diseases	CDE	Draft	20/09/2023	/
3	ICH S12 Guideline on Nonclinical Biodistribution Considerations for Gene Therapy Products	ICH & NMPA	In force	05/09/2023	05/09/2023
4	Technical Guidelines on Pharmacokinetic-based Criteria for Supporting Alternative Dosing Regimens of Programmed Cell Death Receptor-1 (PD-1) or Programmed Cell-ligand 1 (PD-L1) Blocking Antibodies for Treatment of Patients with Cancer	CDE	Draft	01/08/2023	/
5	Technical Guidelines on Nonclinical Study on Therapeutic Radiopharmaceuticals	CDE	Draft	26/06/2023	/
6	Technical Guidelines for Drug Research Based on Animal Rule (Trial)	CDE	In force	07/04/2023	07/04/2023
7	ICH Guideline S1B (R1) on Testing for Carcinogenicity of Pharmaceuticals	ICH & NMPA	In force	22/03/2023	22/03/2023
8	ICH Guideline E14/S7B: Clinical and Nonclinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential-Questions and Answers	ICH & NMPA	In force	22/03/2023	22/03/2023
9	Technical Guidelines for Nonclinical Pharmacokinetic Study on Liposome Drug Products	CDE	Draft	14/03/2023	/
10	Technical Guidelines on Applying Physiological Pharmacokinetic Model to Pediatric Drug Development	CDE	In force	28/03/2023	28/03/2023
11	Technical Guidelines on Nonclinical Studies on Drug Immunotoxicity	CDE	Draft	30/09/2022	/

Chemistry, Manufacturing, and Controls (CMC)

No	Guidelines	Authority	Status	Issued	Enforced
1	Technical Guidelines on Chemistry, Manufacturing, and Controls Studies on Generic Oral Solutions	CDE	Draft	28/09/2023	/
2	Technical Guidelines on Chemistry, Manufacturing, and Controls Studies on Low Molecular Weight Heparins (LMWHs)	CDE	Draft	28/09/2023	/
3	Technical Guidelines on Chemistry, Manufacturing, and Controls Studies on Chemical Suspension for Nasal Spray	CDE	Draft	28/09/2023	/
4	Technical Guidelines on Chemistry, Manufacturing, and Controls Studies on Radioactive Generic Drugs	CDE	Draft	28/09/2023	/
5	Technical Guidelines on Chemistry, Manufacturing, and Controls Research on Mini-tablets (Chemical Drugs)	CDE	Draft	20/09/2023	/
6	Technical Guidelines on Chemistry, Manufacturing, and Controls Changes to Chemical Drugs with Marketing Authorization (Trial)-Q&As on Changes to Active Pharmaceutical Ingredients	CDE	Draft	01/09/2023	/
7	ICH Guideline Q12 on Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management	ICH & NMPA	In force	25/08/2023	25/08/2023
8	1) Technical Guidelines on the Chemistry, Manufacturing and Controls Change and Research on Biologics During Clinical Trial 2) Technical Guidelines on Chemistry, Manufacturing, and Controls Post-approval Changes of Vaccines	CDE	Draft	28/08/2023	/
9	Technical Guidelines on Chemistry, Manufacturing, and Control Studies on TCM Combination Preparations	CDE	In force	25/07/2023	25/07/2023
10	Technical Guidelines on Chemistry, Manufacturing, and Controls Study and Evaluation for Clinical Trials for In Vivo Gene Therapy with Adeno-associated Virus as a Vector	CDE	Draft	25/07/2023	/
11	Technical Requirements for Chemistry, Manufacturing, and Controls Studies on the Generics of 18F-fludeoxyglucose Injection	CDE	Draft	20/06/2023	/
12	Technical Requirements for Chemistry, Manufacturing, and Controls Studies on the Generics of 18F-fludeoxyglucose Injection	CDE	Draft	20/06/2023	/
13	Technical Guidelines on Chemistry, Manufacturing, and Controls Study and Evaluation of Antibody-Drug Conjugates (ADCs)	CDE	Draft	21/06/2023	/
14	Questions & Answers—Studies on Chemistry, Manufacturing, and Control (CMC) Changes to Chimeric Antigen Receptor (CAR) T Cell Therapeutic Products	CDE	Draft	26/06/2023	/
15	Implementation Advice on ICH Guideline Q13 on Continuous Manufacturing of Drug Substances and Drug Products, and the Chinese version of the Guideline	ICH & CDE	Draft	10/05/2023	/
16	Technical Guidelines on Chemistry, Manufacturing, and Controls Study and Evaluation of Human Stem Cell Products (Trial)	CDE	In force	27/04/2023	27/04/2023
17	Technical Guidelines on Quality Control for Liposome Drug Products	CDE	Draft	14/03/2023	/
18	Technical Guidelines on Chemistry, Manufacturing, and Controls Study for Preventing Misuse of Opioid Oral Dosage Forms	CDE	In force	17/03/2023	17/03/2023
19	Technical Guidelines on Consecutive Manufacturing of Chemical Oral Dosage Forms (Trial)	CDE	In force	21/03/2023	21/03/2023
20	Technical Guidelines on Platform Validation for Sterilization and Virus-extermination for Recombinant Biological Technology Products for Treatment	CDE	Draft	22/03/2023	/
21	Common Chemical, Manufacturing, and Controls Issues and Technical Requirements for Meetings Prior to the Phase III Clinical Trials for Innovative Chemical Drugs	CDE	In force	24/03/2023	24/03/2023
22	Technical Guidelines on Chemistry, Manufacturing, and Controls (CMC) Study and Evaluation of Oncolytic Virus Products (Trial)	CDE	In force	13/02/2023	13/02/2023
23	Technical Guidelines for Quality Attribute Researches on Chewable Tablets (Chemical Drugs) (Trial)	CDE	In force	14/02/2023	14/02/2023
24	Technical Guidelines for Chemistry, Manufacturing, and Controls Study on Generic Chemical Ophthalmic Solution	CDE	In force	16/02/2023	16/02/2023
25	Technical Guidelines on Microbial Limit Researches for Non-sterile Chemical Drugs, Active Pharmaceutical Ingredients, and Excipients (Trial)	CDE	In force	21/02/2023	21/02/2023
26	Technical Guidelines on Chemistry, Manufacturing, and Controls Researches on Chemically Synthesized Peptide Drug Products	CDE	In force	21/02/2023	21/02/2023
27	ICH Q3D (R2) Guideline on Elemental Impurities	ICH & NMPA	In force	29/01/2023	29/01/2023
28	Technical Guidelines on the Chemistry, Manufacturing, and Controls (CMC) Study on Alcohol-induced Dose Dumpling (ADD) Trial for Oral Modified-release Generic Drug	CDE	In force	08/11/2022	08/11/2022
29	Q&A on Dissolution Profile in the "Technical Guidelines on Researches on Chemistry, Manufacturing, and Controls (CMC) Changes to Approved Drugs (Trial)"	CDE	In force	08/11/2022	08/11/2022
29	ICH Guideline Q5A(R2) on Viral Safety Evaluation of Biotechnology and its Chinese Translation	ICH & CDE	Draft	28/11/2022	/
30	Technical Guidelines on Chemical Synthetic Peptide Drugs' Chemistry, Manufacturing, and Control (CMC) Researches	CDE	Draft	25/10/2022	/
31	Technical Guidelines on Chemistry, Manufacturing, and Controls (CMC) Studies for Preventing the Abuse of Generic Solid Oral Opioid Drugs	CDE	Draft	05/09/2022	/

Clinical Research

No	Guidelines	Authority	Status	Issued	Enforced
1	Technical Guidelines on Evaluating Clinical Therapeutic Efficacy of New Traditional Chinese Medicines for Tension Headache	CDE	Draft	28/09/2023	/
2	Technical Guidelines on Clinical Trials for Therapeutic Drugs for Dry Eyes	CDE	Draft	28/09/2023	/
3	Technical Guidelines on Clinical Trials for Therapeutic Drugs for Multiple Sclerosis	CDE	Draft	28/09/2023	/
4	Technical Guidelines on Clinical Trials for Drugs for Treating Lupus Nephritis	CDE	Draft	28/09/2023	/
5	Technical Guidelines on Clinical Trials for Drugs for Slowing the Progression of Chronic Renal Diseases	CDE	Draft	28/09/2023	/
6	Technical Guidelines on Clinical Trials for Growth Hormones for Treating Growth Hormone Deficiency	CDE	Draft	25/09/2023	/
7	Technical Guidelines on Clinical Trials for Mesenchymal Stem Cells for Preventing and Treating Graft-versus-host Diseases	CDE	Draft	12/09/2023	/
8	Technical Guidelines on Clinical Trials for Gene Therapies for Rare Diseases	CDE	Draft	12/09/2023	/
9	Technical Guidelines on Clinical Trials for Human Fibrinogen (Revision)	CDE	Draft	04/09/2023	/
10	Guidelines on the R&D of Oral Combination Drugs for Type-2 Diabetes Mellitus	CDE	In force	02/08/2023	02/08/2023
11	1) Technical Guidelines on Designing Patient-centered Clinical Trials for Drugs (Trial) 2) Technical Guidelines on Conducting Patient-centered Clinical Trials for Drugs (Trial) 3) Technical Guidelines on Patient-centered Benefit-risk Assessment of Drugs (Trial)	CDE	In force	02/08/2023	02/08/2023
12	Guidelines on Identifying, Handling, and Evaluating Drug-induced Liver Injury in Clinical Trials	CDE	In force	10/07/2023	10/07/2023
13	Technical Guidelines on Clinical Trials for Human Papillomavirus (HPV) Vaccines (Trial)	CDE	In force	11/07/2023	11/07/2023
14	Technical Guidelines on Making Investigational Drugs for New TCMs’ Clinical Trials (Trial)	CDE	In force	25/07/2023	25/07/2023
15	Technical Guidelines on Clinical Development of New TCMs for Diabetic Retinopathy	CDE	Draft	17/07/2023	/
16	Technical Guidelines on Human Radiolabeled Mass Balance Studies	CDE	Draft	24/07/2023	/
17	Technical Guidelines on Pharmacological Studies on Improved Chemical Drugs	CDE	Draft	28/07/2023	/
18	Technical Guidelines on the Clinical Trial Design for the New Non-opioid Analgesics for Postoperative Pain	CDE	In force	09/06/2023	09/06/2023
19	Technical Guidelines on Clinical Trials for Human Stem Cell and Stem Cell-derived Therapeutic Products	CDE	In force	21/06/2023	21/06/2023
20	Technical Guidelines on Applying Patient Report Outcomes (PROs) to Clinical Trials for Autoimmune Rheumatic Diseases (ARDs)	CDE	Draft	27/06/2023	/
21	ICH E6(R3) Guideline for Good Clinical Practice (GCP)	ICH & CDE	Draft	29/05/2023	/
22	Technical Guidelines on Clinical R&D of Antibody-Drug Conjugates (ADCs)	CDE	In force	07/04/2023	07/04/2023
23	Guidelines on Qualitative Methodology for Extrapolation of Medicine Use Data from Adults to Pediatric Patients (Trial)	CDE	In force	12/04/2023	12/04/2023
24	Technical Guidelines on Clinical Trials for Drugs for Respiratory Syncytial Virus (RSV) Infection	CDE	In force	12/04/2023	12/04/2023
25	Technical Guidelines on Clinical Trial Design for Gene Therapy for Hemophilia	CDE	In force	14/04/2023	14/04/2023
26	Technical Guidelines on Clinical R&D of New Combination TCMs for Treating Malignant Tumors (Trial)	CDE	In force	14/04/2023	14/04/2023
27	Technical Guidelines on Clinical Trials for Active Immunotherapy Products for Tumor (Trial)	CDE	In force	26/04/2023	26/04/2023
28	Technical Guidelines on Clinical Trials for Therapeutic Drugs for Chronic Hepatitis B Virus (HBV) Infection	CDE	In force	27/04/2023	27/04/2023
29	Technical Guidelines on Clinical R&D on the Antineoplastic Photodynamic Therapeutic Drugs (Trial)	CDE	In force	28/04/2023	28/04/2023
30	Technical Guidelines on Clinical Endpoints for Advanced Prostate Cancer	CDE	In force	14/03/2023	14/03/2023
31	Technical Guidelines on the Applicability of Single-arm Clinical Trials to Support Marketing Authorization Application of Anti-neoplastic Drugs	CDE	In force	14/03/2023	14/03/2023
32	Technical Guidelines on Clinical Trials for Chemical Combination Drug Products	CDE	In force	17/03/2023	17/03/2023
33	Technical Guidelines on Clinical Development of New Drugs for Treating Ovarian Cancer	CDE	In force	21/03/2023	21/03/2023
34	Technical Guidelines on Clinical Trials for Pediatric Anti-neoplastic Drugs	CDE	In force	24/03/2023	24/03/2023
35	Technical Guidelines on Clinical R&D of New Drugs for Acute Myeloid Leukemia (AML)	CDE	In force	13/02/2023	13/02/2023
36	Technical Guidelines on Clinical Trials for Therapeutic Drugs for Primary Biliary Cholangitis (PBC)	CDE	In force	13/02/2023	13/02/2023
37	Technical Guidelines on Clinical Evaluation of In Vivo Therapeutic Radiopharmaceuticals	CDE	In force	15/02/2023	15/02/2023
38	Technical Guidelines on Clinical R&D of Type-2 Diabetes Mellitus Drugs for Adults	CDE	In force	21/02/2023	21/02/2023
39	Clinical R&D Guidelines on New Drugs for Chronic Lymphocytic Leukemia	CDE	Draft	19/01/2023	19/01/2023
40	Technical Guidelines on Evaluating Clinical Efficacy of New Traditional Chinese Medicines (TCM) for Chronic Gastritis (Trial)	CDE	In force	21/12/2022	21/12/2022
41	Technical Guidelines on Evaluating Clinical Efficacy of New TCMs for Gastroesophageal Flux Disease (Trial)	CDE	In force	21/12/2022	21/12/2022
42	Guidelines on Immunobridging Clinical Trials for Prophylactic Vaccines	CDE	Draft	21/12/2022	21/12/2022
43	Guidelines on Blind Clinical Trials for Drugs (Trial)	CDE	In force	30/12/2022	30/12/2022
44	Technical Guidelines on the Clinical Development of Bispecific Antibody Drugs for Cancer	CDE	In force	14/11/2022	14/11/2022
45	Technical Guidelines on Clinical Trials for Drugs Treating Chronic Kidney Diseases	CDE	Draft	16/11/2022	/
46	Technical Guidelines on Clinical Trials for Drugs Treating Atopic Dermatitis	CDE	Draft	18/11/2022	/
47	Technical Guidelines on Clinical trials for Therapeutic Vaccines for Cancer	CDE	Draft	09/10/2022	/
48	Technical Guidelines on Clinical Safety Evaluation of New Drugs	CDE	Draft	25/10/2022	/
49	Work Rules for Reviewing Drug Clinical Trial Protocols	CDE	Draft	27/10/2022	/
50	Technical Guidelines on Clinical Trials for Combination Drugs	CDE	Draft	07/09/2022	/
51	Technical Guidelines on Drugs' Clinical Dependence Studies	CDE	In force	28/09/2022	28/09/2022

Real-world Evidence

No	Guidelines	Authority	Status	Issued	Enforced
1	Guidelines on Design and Protocol of Drug Real-world Evidence Study (Trial)	CDE	In force	16/02/2023	16/02/2023
2	Guidelines on Communication About Drug Registration Applications Supported by Real-world Evidence	CDE	In force	16/02/2023	16/02/2023

Bioequivalence

No	Guidelines	Authority	Status	Issued	Enforced
1	1) Technical Guidelines for Bioequivalence Studies on Azathioprine Tablets 2) Technical Guidelines for Bioequivalence Studies on Mercaptopurine Tablets 3) Technical Guidelines for Bioequivalence Studies on Regorafenib Tablets 4) Technical Guidelines for Bioequivalence Studies on Octreotide Acetate Microspheres for Injection 5) Technical Guidelines for Bioequivalence Studies on Omeprazole and Sodium Bicarbonate Capsules 6) Technical Guidelines for Bioequivalence Studies on Omeprazole and Sodium Bicarbonate for Suspension	CDE	Draft	22/08/2023	/
2	1) Guidelines on Bioequivalence of Acetylcysteine Granules 2) Guidelines on Bioequivalence of Etomidate Injectable Emulsion 3) Guidelines on Bioequivalence of Epalrestat Tablets 4) Guidelines on Bioequivalence of Thioctic Acid Tablets 5) Guidelines on Bioequivalence of Lidocaine and Prilocaine Cream	CDE	Draft	27/07/2023	/
3	ICH Guideline M13A: Bioequivalence for Immediate-release Solid Oral Dosage Forms and its Chinese Translation	ICH & CDE	Draft	14/02/2023	/
4	Technical Guidelines on Bioequivalence Studies on Tenofovir Alafenamide Fumarate Tablets	CDE	In force	25/11/2022	25/11/2022
5	Technical Guidelines on Bioequivalence Studies on Loratadine Tablets	CDE	In force	25/11/2022	25/11/2022
6	Technical Guidelines on Bioequivalence Studies on Tadalafil Tablets	CDE	In force	25/11/2022	25/11/2022
7	Technical Guidelines on Bioequivalence Studies on Amphotericin B Liposome for Injection	CDE	In force	25/11/2022	25/11/2022
8	Technical Guidelines on Bioequivalence of Aspirin Enteric-coated Tablets	CDE	In force	09/10/2022	09/10/2022

Equivalence Evaluation for Generics

No	Guidelines	Authority	Status	Issued	Enforced
1	Technical Guidelines on Overfill Studies on Generic Drugs	CDE	Draft	28/09/2023	/
2	Guidance for the Acceptance Review of Quality and Therapeutic Equivalence Evaluation Applications for Generic Drugs	CDE	Draft	25/09/2023	/

Pharmacovigilance

No	Guidelines	Authority	Status	Issued	Enforced
1	Technical Guidelines on Evaluating the Relevance of Adverse Events During Clinical Trials for Drugs	CDE	Draft	26/09/2023	/
2	CDE Work Procedures for Safety Information Assessment and Risk Management During Clinical Trials for Drugs (Trial) (Revised)	CDE	Draft	10/07/2023	/
3	Technical Guidelines on Writing Safety Information for Medication Package Inserts of Antineoplastic Drugs	CDE	Draft	30/06/2023	/
4	ICH E19: Selective Approach to Safety Data Collection in Specific Late-stage Pre-approval or Post-approval Clinical Trials	ICH	In force	24/04/2023	21/10/2023
5	Guidelines on the Summary, Analysis, and Report of Safety Information During Clinical Trial for Drugs	CDE	In force	17/03/2023	17/03/2023
6	FAQ on Immediate Report of Safety Data During Drug Clinical Trials (Version 2.0)	CDE	In force	17/03/2023	17/03/2023

Communication with CDE

No	Guidelines	Authority	Status	Issued	Enforced
1	Dossier Requirements for Communication Applications	CDE	Draft	18/09/2023	/
2	Opinions on Accelerating the Communication about and Application of TCM Combination Preparations Originated from Ancient Classic Prescriptions	CDE	Draft	05/07/2023	/
3	Technical Guidelines on Communications About Clinical Studies on Cell and Gene Therapies	CDE	Draft	25/07/2023	/
4	Detailed Rules on the Administrative Work and Application of Type I Meetings for Communication on Pediatric Drugs (Trial)	CDE	In force	18/04/2023	18/04/2023

Quality Risk Management

No	Guidelines	Authority	Status	Issued	Enforced
1	ICH Q9 (R1) Guideline on Quality Risk Management	ICH & NMPA	In force	05/09/2023	04/03/2024

Impurity Study

No	Guidelines	Authority	Status	Issued	Enforced
1	ICH M7(R2) Guideline on Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk, its Questions and Answers, Addendum, as well as the Chinese versions of these documents	ICH & CDE	Draft	25/08/2023	/

Method Validation

No	Guidelines	Authority	Status	Issued	Enforced
1	ICH Guideline M10 on Bioanalytical Method Validation and Study Sample Analysis-Q&As and FAQs	ICH & NMPA	In force	04/07/2023	29/07/2023
2	ICH M10 Guideline on Bioanalytical Method Validation	ICH & NMPA	In force	29/01/2023	29/01/2023

Natural History Study

No	Guidelines	Authority	Status	Issued	Enforced
1	Guidelines on Natural History Studies for the Development of Rare Disease Drugs	CDE	In force	27/07/2023	27/07/2023

Marketing Authorization Application

No	Guidelines	Authority	Status	Issued	Enforced
1	Guidance for the Acceptance Review of Marketing Authorization Applications of Chemical Drugs’ Active Pharmaceutical Ingredients (Trial)	CDE	In force	03/07/2023	03/07/2023

Drug Registration Dossier Requirement

No	Guidelines	Authority	Status	Issued	Enforced
1	Technical Requirements for the Electronic Compact Disks Containing Application Dossiers	CDE	Draft	07/07/2023	/
2	Guidance for Electronic Common Technical Document (eCTD) Implementation V1.1	CDE	Draft	29/01/2023	/
3	Standards for eCTD Validation V1.1	CDE	Draft	29/01/2023	/

Post-approval Change

No	Guidelines	Authority	Status	Issued	Enforced
1	Work Procedures for Adding Pediatric Information to the Medication Package Inserts of Approved Drugs (Trial)	CDE	In force	04/07/2023	04/07/2023

Online Sales

No	Guidelines	Authority	Status	Issued	Enforced
1	Guidelines on Inspections of Third-party Platforms for Drug Transactions Online	NMPA	Draft	06/09/2023	/

Benefit-risk Assessment

No	Guidelines	Authority	Status	Issued	Enforced
1	Technical Guidelines on Benefit-risk Assessment for New Drugs	CDE	In force	25/06/2023	25/06/2023

Label

No	Guidelines	Authority	Status	Issued	Enforced
1	Writing Guidelines on Chemistry, Manufacturing, and Controls Information on Chemical Drugs’ Medication Package Inserts and Labels	CDE	In force	21/03/2023	21/03/2023

Multidisciplinary

No	Guidelines	Authority	Status	Issued	Enforced
1	ICH M11 Guideline on Clinical Electronic Structured Harmonized Protocol (CeSHarP), its technical specifications, Chinese translation, and implementation advice	ICH & CDE	Draft	06/01/2023	/
2	Technical R&D Guidelines on Improved Traditional Chinese Medicines	CDE	Draft	06/01/2023	/
3	Technical Guidelines on Researches on TCM Having the Same Name and Formulation With an Approved TCM (Trial)	CDE	In force	27/12/2022	27/12/2022
4	Technical Guidelines on the Design and Evaluation of the Taste of Pediatric Drugs	CDE	In force	02/11/2022	02/11/2022
5	Guidelines on General Considerations for Patients' Engagement in Drug Development (Trial)	CDE	In force	25/11/2022	25/11/2022

BaiPharm consultants are experienced in helping pharma companies register medical products and keep compliant with post-marketing regulations. Don’t hesitate to contact us if you need support in understanding and implementing China’s pharma guidelines.