Substandard medicines categorised by manufacturers The review identified 122 licensed manufacturers and 26 licensed distributors. Manufacturers held the marketing authorisation for 611 substandard medicines and distributors for 38 (table 4). No unlicensed manufacturers or distributors were involved. A comparison between those manufacturers and distributors in the number learn more of substandard medicines reported under each defect type and the p values for these differences is presented
in table 4. No significant differences were observed between manufacturers and distributors. Table 4 Substandard medicines categorised by type of marketing authorisation holders The top 20 manufacturers are listed in online supplementary table SS4.4. It was noted that 50% or more of substandard medicines manufactured by Apotex Inc, Pfizer Canada Inc and Laboratoire Riva Inc had stability issues. Almost half of the substandard products from Baxter Co, Hospira Healthcare Co and GlaxoSmithKline Inc were contaminated. Products of Sandoz Canada Inc had a problem with the active ingredient; the concentration was either too high
or too low. More than half of Novartis products, which are reported to be substandard, were recalled due to delivery concerns, such as failure of the child-resistant feature of the bottle cap or leaks in the infusion bags. Falsified medicines Four incidents of falsified medicines were identified in Canada’s supply chain between 2010 and 2013. All these incidents involved two sexual enhancement medicines, Viagra (sildenafil) and Cialis (tadalafil). In all cases of falsified medicines, PAs were issued to inform the public to contact their healthcare professionals if they had concerns about these falsified medicines. The public was also advised to verify that these products were assessed by Health Canada for safety by looking at the authorisation number printed on the label. These medicines were
seized in the retail outlets in Canada, and no further information was given by Health Canada about the subsequent investigation or action taken by Health Canada. Discussion This is the first review that discusses the issue of substandard Cilengitide and falsified medicines in Canada by evaluating the risk communication documents and drug recalls posted on Health Canada website. Our observations of defective medicines recalls over nine consecutive years, from 2005 to 2013, have shown that the recall of substandard medicines is an increasing trend. It is concerning that over half of the stability failures were related to instability of active ingredients or dissolution and disintegration failure. Both defects have the potential to affect the bioavailability of the active ingredients in the systemic circulation, and in turn, may lead to therapeutic failure. Substandard medicines The most frequent type of formulation reported to be substandard were tablets.