The Pharmaceutical Industry: History, Structure, and Challenges

Part 1: Story

In 1960, Frances Oldham Kelsey joined the U.S. Food and Drug Administration (FDA) as a medical reviewer.

One of her first assignments was an application to market thalidomide in the United States. The sedative was already used in other countries, including by some pregnant patients.

Kelsey and colleagues found the evidence of safety inadequate and asked the applicant for more information, including about reported nerve damage. The FDA did not approve the application.

The drug was subsequently linked to severe birth defects in thousands of children internationally. The United States did not approve its commercial sale, although some U.S. patients had received it through investigational distribution.

The episode helped build support for the 1962 Kefauver–Harris Drug Amendments. U.S. law had already required evidence of safety for new drugs; the amendments added a requirement to demonstrate effectiveness and strengthened oversight of clinical investigations.

The law is a milestone in U.S. drug regulation, but it did not alone determine global R&D costs or create the industry’s market structure. Today’s long development cycles reflect scientific uncertainty, testing, manufacturing, regulation, and commercialization together.

Part 2: Industry History

The modern pharmaceutical industry developed across more than a century of chemical synthesis, biological research, large-scale manufacturing, clinical testing, and regulation. The timeline below is a simplified guide, not a claim that innovation or manufacturing was confined to the United States and Europe.

1. Late 19th Century - 1930s: From Dye Workshops to Chemical Synthesis (Disorderly Emergence)

Plant Extraction and Accidental Discovery.

Bayer is one example of the connection between synthetic-dye manufacturing and pharmaceutical development. Its company history records a pharmaceutical department in 1888 and the launch of Aspirin in 1899. Bayer joined I.G. Farben in 1925. This company account illustrates one path into pharmaceuticals; it does not establish a single origin for the whole industry or the absence of clinical investigation in that period.

2. 1940s - 1960s: Mass Production of Antibiotics and the Iron Curtain of Regulation (Foundational Period)

Bacterial Culture and Large-Scale Random Screening.

During World War II, Pfizer helped scale penicillin production using deep-tank fermentation; in 1962, the U.S. passed the Kefauver–Harris Drug Amendments amid the thalidomide crisis.

Large-scale antibiotic production helped develop fermentation and purification capabilities. The 1962 amendments reinforced the evidence required for new-drug approval in the United States; they did not by themselves eliminate smaller manufacturers or establish an oligopoly.

3. 1970s - 1990s: The Era of Molecular Biology and Blockbuster Drugs (The Golden Age of Profits)

Target-Based Drug Discovery.

The lipid-lowering drug Lipitor and the antidepressant Prozac were launched.

With a better understanding of receptors and enzymes, target-based discovery became more important alongside screening and empirical methods. Medicines for common chronic diseases supported a blockbuster model, although sales and margins differ markedly by product and company.

4. 2000s - 2010s: The Biomolecular Revolution and Restructuring of Specialization

Recombinant DNA technology and monoclonal antibodies (mAbs).

Products such as Humira illustrated the commercial potential of biologics. Researchers also debated the long-run productivity of drug R&D, sometimes calling the observed trend “Eroom’s Law.”

Biotechnology firms such as Genentech helped bring biologics into mainstream development. Many large firms now combine in-house R&D with licensing and acquisitions; smaller firms and large manufacturers can each participate at multiple stages of development.

5. 2020s to Present: Multimodal, Precision Medicine, and Computational Drug Development

Programmable drugs (mRNA, ADC, CGT) and AI-driven computing (AIDD).

mRNA vaccines were rapidly developed and launched during the COVID-19 crisis; AI structural biology tools such as AlphaFold have achieved widespread penetration; ADCs (antibody-drug conjugates) have become the mainstay of precision oncology.

Computational methods increasingly complement laboratory and clinical work. In some disease areas, biomarker-guided treatments supplement broad-market products; computational predictions do not replace experimental validation.

Similarly, the pharmaceutical industry, like its history, is extremely complex. Let’s break it down simply:

Part 3: Industry Structure

The pharmaceutical industry is a complex and unique industry characterized by high technological barriers, high compliance thresholds, long cycles, high profit margins, and high risks. The entire industry chain can be clearly divided into three core segments: upstream (R&D support), midstream (pharmaceutical companies and product portfolios), and downstream (distribution, channels, and payers).

I. Upstream: R&D and Production Support (“Water Sellers” and Infrastructure)

The upstream provides pharmaceutical companies with comprehensive services from target discovery and experimental consumables to contract manufacturing. It is a relatively risk-dispersed and cash-flow-stable “water-selling” segment. It is divided into four complex parts:

1. Scientific Reagents and High-End Instruments

   • Core Functions and Roles: Providing gene sequencers, high-resolution mass spectrometers, culture media, biochips, and laboratory consumables; it is the “arsenal” of pharmaceutical R&D.
   • Representative companies/institutions: Thermo Fisher Scientific, Danaher, Merck KGaA, Illumina

2. Active Pharmaceutical Ingredients (APIs) & Intermediates

   • Core Functions and Roles: Providing active pharmaceutical ingredients (APIs) and key chemical intermediates. Divided into bulk APIs (such as vitamins and antibiotics) and specialty/high-difficulty APIs.
   • Representative companies/institutions: Zhejiang Medicine, Huahai Pharmaceutical, Lonza, Teva (API division)

3. CXO (Contract Research and Development Organization)

   • Core Functions and Roles: CRO (Contract Research Organization) assists in preclinical and clinical trials; CDMO/CMO (Contract Development and Manufacturing Organization) assists in process development and commercial mass production.
   • Representative companies/institutions: WuXi AppTec, Pharmaron, Tigermed, Lonza, Catalent

4. AI Computing Power and Cutting-Edge Technology Platform

   • Core Functions and Roles: Provides gene editing tools, protein structure prediction, and AI drug molecular screening platform (AIDD).
   • Representative companies/institutions: Schrödinger, Recursion Pharma, Insilico Medicine

II. Midstream: Pharmaceutical Companies and Product Matrix (Core Value Creators and Risk Bearers)

The midstream is the main body of the pharmaceutical industry, bearing the most significant financial risks in drug development and being the primary beneficiaries of patent monopoly premiums. It can be broken down into four camps based on business models:

1. Big Pharma (Multinational Traditional Giants)

   • Business Model: In-house research + external mergers and acquisitions (M&A) / licensing introduction.
   • Core Barriers: Extensive global clinical trial compliance capabilities, a global commercial sales network, and abundant cash flow.
   • Representative companies: Pfizer, Eli Lilly, Novartis, Merck (MSD), AstraZeneca.

2. Biotech (Innovative Biotechnology Companies)

   • Business Model: Focuses on specific cutting-edge targets or new technology platforms (such as ADC, mRNA, CAR-T). They typically lack a mature sales force, and after reaching Phase II clinical trials, they often choose to sell their rights to a Big Pharma or be directly acquired.
   • Core Barriers: The R&D efficiency of top scientists and patent protection.
   • Representative companies: BioNTech, Moderna, BeiGene, Sarepta.

3. Generic Pharma (Generic Drug Companies)

   • Business Model: Involves rapidly following up on original drug patents after they expire (Paragraph IV challenge), achieving large-scale substitution at extremely low cost.
   • Core Barriers: Extremely high production cost control, ability to tackle complex formulations, and rapid supply chain response capabilities.
   • Representative companies: Teva, Sandoz, Viatris, Sun Pharma.

4. Specialty Pharma

   • Business Model: Avoid the fierce competition of Big Pharma in areas like oncology and cardiovascular diseases, and instead focus on niche markets such as ophthalmology, dermatology, central nervous system (CNS), or rare diseases.
   • Representative companies: Santen (ophthalmology), Jazz Pharmaceuticals (rare diseases/sleep disorders).

III. Downstream: Distribution, Channels, and Payers (Commercial Monetization and Value Loop)

After drugs are produced, they must be delivered to end users through an efficient supply chain and monetized through a specific payment system.

1. Pharmaceutical Distributors

   • Role: Warehousing, distribution, financing, and channel management between pharmaceutical companies and end users.
   • Business characteristics: Often relies on scale and efficient working-capital turnover; margins differ by contract and reporting basis.
   • Representative companies:
     • Large U.S. distributors include McKesson, Cencora (formerly AmerisourceBergen), and Cardinal Health.
     • Chinese giants: Sinopharm, Shanghai Pharmaceuticals, China Resources Pharmaceutical, and Jointown Pharmaceutical Group.

2. End Channels

   • Hospital Market (HCOs): Public/private hospitals. The core market for the vast majority of prescription drugs, injectables, and critical care medications.
   • Retail & DTP Pharmacies: Chain pharmacies, DTP (Direct to Patient) high-value prescription pharmacies, and online pharmacy platforms (such as JD Health and Meituan Pharmacy).

3. Payers & Access – The Industry’s “Life and Death Power”

   • Public financing and procurement (varies by country): In China, the National Healthcare Security Administration (NHSA) plays a central role in reimbursement and procurement; the National Medical Products Administration (NMPA) regulates medicines. European payment systems differ substantially by country.
   • Multi-payer model (US market): Commercial insurance companies (UnitedHealth, Anthem, etc.) and PBMs (Pharmacy Benefit Managers, such as CVS Caremark, Express Scripts) hold the power of life and death over whether a drug can be included in the reimbursement list. PBMs, by controlling a massive number of patient payments, force pharmaceutical companies to offer substantial rebates.

IV. The Underlying Operating Mechanism of the Industry Chain: “Patent Cliff” and Value Cycle

The flow of funds and value throughout the pharmaceutical industry chain is driven by the lever of “patent protection.”

New drug R&D investment -> regulatory approval and a period of market exclusivity where applicable -> patent or exclusivity expiry -> potential generic or biosimilar competition -> reinvestment in development. Prices and the duration of effective exclusivity vary by product and jurisdiction.

1. Biotech companies undertake high-risk breakthroughs in the early stages;
2. CXOs earn fixed service fees;
3. Large firms may use capital and commercial networks to launch medicines across markets during their remaining effective exclusivity;
4. After patent expiration, generic drug companies and distributors quickly take over the market, significantly reducing healthcare costs, while Big Pharma uses its profits to seek the next biotech target, completing the cycle.

Of course, high returns often come with high risks. This complex competitive landscape limits drug development efficiency and triggers various commercial struggles and public health crises.

Where medicines are sold

The regional sales mix below describes 2025 retail and hospital prescription medicine sales at ex-manufacturer prices, using IQVIA MIDAS figures reproduced in EFPIA’s The Pharmaceutical Industry in Figures — Key Data 2026, page 14. These are geographic sales destinations, not manufacturers’ headquarters or pharmaceutical-company market shares. The DEX CSV is a derivative export of this chart, not independent primary verification.

Part 4: Industry Issues and Challenges

1. The “Eroom’s Law” of R&D Efficiency

R&D productivity is difficult to measure: The term “Eroom’s Law” describes a historical observation that research spending rose faster than some measures of output; its rate depends on the period and method used.

1. Scientific and clinical uncertainty: Some targets are difficult to validate, trials are expensive, and projects can fail at any stage. A single “time to market” or cost figure does not represent all medicines.

2. Commercial Incentives and Public Health Needs: Severe Mismatch in Public Health Needs

Commercial incentives do not always match public-health needs: Expected revenue influences private investment, but clinical feasibility, public funding, and regulation also shape which therapies advance:

• New Antibiotic Crisis: Given the small dosage, short duration of use, and ease of developing drug resistance, pharmaceutical companies cannot recoup their R&D costs, leading to the bankruptcy of many biotech companies developing antibiotics. The world is facing the threat of untreatable superbugs.
• Rare and Tropical Diseases Forgotten: Diseases with extremely small patient populations or very low affordability are unlikely to attract commercial R&D funding.

3. Distorted Intermediary Rent-Seeking and High Drug Prices

Pricing and intermediary incentives: U.S. pharmacy benefit managers (PBMs) negotiate formularies and rebates for payers. Whether rebate arrangements raise list prices or out-of-pocket costs depends on plan design and contract terms; it cannot be assumed that intermediaries capture the majority of every price increase.

4. Geopolitics and Global Supply Chain Vulnerability

API and intermediate supply: Some important supply chains are geographically concentrated. Their resilience depends on product-specific manufacturing capacity, sourcing and inventories; a blanket country share or impact estimate requires a defined dataset.

Source notes and primary materials

• FDA: Frances Oldham Kelsey and the thalidomide application — supports the opening history; it does not establish an exact modern industry-wide R&D cost.
• Kefauver–Harris Drug Amendments, Public Law 87-781 (1962) — approved October 10, 1962, 76 Stat. 780–796. The original U.S. statute supports the safety/effectiveness and clinical-investigation history; it is not a global law. The 17-page scan ends on a shared page that also begins unrelated Public Law 87-782; that next law is not evidence for drug regulation.
• Pfizer: company history — self-authored company account of 1941 penicillin-production efforts and 1944 mass production using deep-tank fermentation; not an independent industry-wide history.
• Bayer: The History of Bayer — current timeline — the current company history was inspected and supports the scoped dye-business, pharmaceutical-department, Aspirin, and 1925 merger example. It is a separate verified destination; the original blocked historical URL remains labelled below.
• Cencora: AmerisourceBergen becomes Cencora — official August 30, 2023 release confirming the completed name and ticker change; supports the naming claim only.

Reference review: 2026-10-03. The accompanying Pharmaceutical Manufacturing working note is a reading list, not an independently verified market dataset. The claim-level sources above are distinguished from research portals, commercial databases, and publication homepages below. Unverified figures have been removed rather than attributed to the note; an accessible homepage does not verify a particular drug, trial, article, or statistic.

View or download the supplied original

The final scanned page contains the end of Public Law 87-781 and the beginning of unrelated Public Law 87-782. Only the Drug Amendments portion supports this article’s regulatory-history discussion.

Links contained in the Pharmaceutical Manufacturing research note

These are the note’s reading leads, not independent verification of every claim or an endorsement of paid databases. Destinations and scope were reviewed on 2026-10-03. Two links that pointed through Google searches are shown as direct destinations; repeated references share the same underlying source. An unresolved access or content check does not establish that a link is dead.

Regulation and trials:

• Drugs@FDA — official search portal and direct destination of the note’s search link; no particular drug result or approval was verified by checking its homepage.
• China’s CDE — official NMPA Center for Drug Evaluation research portal; use a specific notice or review record for a claim-level citation.
• European Medicines Agency — redirects to the official English homepage; an institutional research lead, not a specific medicine or regulatory decision.
• ClinicalTrials.gov — official NLM trial-search and registration portal. Registration is not proof of efficacy or regulatory approval, and the U.S. government does not review or approve the safety and science of every listed study.
• Chinese Clinical Trial Registry — trial-search and registration lead; no individual trial record or result was verified in this review.
• EU Clinical Trials Register — legacy EudraCT records — retains EudraCT trials/results and specified third-country records. Ongoing EU/EEA trials are now displayed through CTIS: search for clinical trials. CTIS supplements the legacy register; it does not replace access to its historical records. Neither portal’s inclusion verifies a particular trial’s results.

Scientific and commercial research:

• DrugBank — commercial drug-data and biopharma-intelligence lead; no licensed dataset, individual molecule claim, or market figure was verified.
• IUPHAR/BPS Guide to Pharmacology — target, ligand, and pharmacology research lead. Its homepage stated that registration is required to use the website; unrestricted access should not be assumed, and no registration was attempted.
• PubChem — NCBI chemical-information search portal; no specific compound record or scientific claim was verified by inspecting the homepage.
• DXY Insight — commercial research-database landing page with trial, registration, marketed-drug, and company-data modules; underlying licensed data and report figures were not inspected.
• FiercePharma — news publication homepage, not a specific article or primary historical, scientific, or market source.
• FierceBiotech — news publication homepage; a specific article and its underlying evidence are needed for a claim-level citation.
• Endpoints News — original reference — Content not confirmed in the 2026-10-03 review. The exact homepage returned HTTP 403; related event pages did not verify its content or provide an equivalent replacement. This access block does not establish deletion.
• BioWorld — direct publication destination of the note’s search link; no particular paid article or dataset was independently inspected.

Historical reading:

• NLM biography of Frances Oldham Kelsey — supports the historical thalidomide-application and regulatory-career account. It does not establish that thalidomide has never subsequently been approved for any indication.
• Bayer’s historical article — original reference — Content not confirmed in the 2026-10-03 review. Bayer’s bot-access block prevented inspection of this path; it is not established to be deleted.
• Current Bayer history timeline — separately inspected company history used for the scoped historical example above; this is a verified current destination, distinct from the original reference.
• Bayer homepage — redirects to the English corporate homepage; company context only, not evidence for a particular historical event.
• Pfizer company history — the same company-authored account cited above, not a second independent historical source.